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Giorgio Vittorio Scagliotti
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PL01 - New Questions with Imaginative Answers (ID 88)
- Event: WCLC 2019
- Type: Plenary Session
- Track: Advanced NSCLC
- Presentations: 4
- Now Available
- Moderators:Enriqueta Felip, Giorgio Vittorio Scagliotti
- Coordinates: 9/08/2019, 08:15 - 09:45, Barcelona (2005)
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PL01.01 - Tumor-Agnostic Biologically Driven Treatments: An Endless Dream? (Now Available) (ID 3580)
08:15 - 09:45 | Presenting Author(s): Robert C. Doebele
- Abstract
- Presentation
Abstract
The identification of several oncogenes in non-small cell lung cancer (NSCLC) along with the development of cognate, targeted tyrosine kinase inhibitors (TKIs) has revolutionized the treatment approach for patients with this disease. Several oncogene targets have been successfully deployed in other malignancies, including melanoma (BRAF), GIST (KIT), CML (BCR-ABL) and other malignancies. However, until recently, the conventional wisdom has said that targeted therapies will not have similar efficacy for the same class of oncogenes across different tumor histologies. This point of view was likely largely grounded in two perceptions: 1) certain oncogenes are heavily associated with certain tumor histologies (e.g., BCR-ABL in CML or EGFR in NSCLC) and 2) based on the differential activity of BRAF/MEK inhibition in melanoma compared to colorectal cancers (CRC) harboring BRAF V600E mutations. Since then, BRAF +/- MEK inhibition has demonstrated remarkable response rates in NSCLC, anaplastic thyroid cancer, and hairy cell leukemia suggesting that CRC may be the exception rather than the rule. In 2012, we identified the first NTRK1 fusion in NSCLC,1 and while prior reports of NTRK gene fusions existed,2 there were no therapies developed for this oncogene. Preclinical in vitro and in vivo models suggested that ATP-competitive inhibitors had activity irrespective of NTRK1/2/3 gene (TRKA/B/C kinases) and also irrespective of tumor histology.3 Clinical trial data with the two lead TRK inhibitors, larotrectinib4 and entrectinib,5 confirmed both of these preclinical findings of activity in NTRK1/2/3 across tumor histologies, validating the concept of tumor (or tissue) agnostic therapeutic strategies in cancer. Similar to NTRK gene fusions, ALK, ROS1 and RET gene fusions have not only been identified in NSCLC, but also in other tumor histologies. Clinical data suggest similar opportunities for these oncogene targets. For examples, entrectinib generated a robust and durable response in a patient with GOPC-ROS1 fusion melanoma6 and similar responses have been noted in ROS1 fusion IMT.7 Basket clinical trials of ROS1 inhibitors are now ongoing. RET gene fusions are targetable alterations in NSCLC as well as other malignancies, and now improved, highly RET-selective inhibitors under development with encouraging activity.8 NRG1 gene fusions represent another opportunity for a tumor agnostic development. Although first described in NSCLC (specifically, invasive mucinous adenocarcinomas),9 these novel fusion genes that signal via HER2/HER3 heterodimers have been described across numerous tumor types, including pancreatic, ovarian, and other cancers, albeit at a low estimated frequency of 0.2%.10 This low frequency is a common reason cited to not pursue such strategies, but given the immense heterogeneity of cancer it is likely that we will further fragment cancer types based on their underlying biology. Additional tumor agnostic targets include ALK gene fusions, HER2 mutations, EGFR mutations (including exon 20 insertions), FGFR1/2/3 fusions, BRAF fusions, MET (exon 14 skipping, gene amplification, and fusions), and others. Indeed, several KRAS mutant selective inhibitors are under development and may open the flood gates for tumor agnostic trials given the frequency of mutations in this oncogene. Success of tumor agnostic strategies will be dictated by appropriate biomarker selection, which may differ for each tumor types, robust testing methods that capture the majority of oncogenic variants (NRG1 is a good example that is not currently covered on many assays), and implementation of panel-based next generation sequencing applications in more routine practice. While it is likely that we already have the testing capability and even the appropriate drugs to to target these tumor agnostic oncogenes, infrastructure changes at institutions may need to be enacted to allow for clinical trial teams that enroll from many disease types, similar to existing phase I teams. The NSCLC community of oncologists, researchers, pathologists, patient advocates, and commercial partners has had immense success in realizing the dream of precision oncology strategies and can lead the way to distribute the knowledge gained over the last decade in precision oncology strategies.
References
1. Vaishnavi A, Capelletti M, Le AT, et al: Oncogenic and drug-sensitive NTRK1 rearrangements in lung cancer. Nat Med 19:1469-1472, 2013
2. Vaishnavi A, Le AT, Doebele RC: TRKing down an old oncogene in a new era of targeted therapy. Cancer Discov 5:25-34, 2015
3. Doebele RC, Davis LE, Vaishnavi A, et al: An Oncogenic NTRK Fusion in a Patient with Soft-Tissue Sarcoma with Response to the Tropomyosin-Related Kinase Inhibitor LOXO-101. Cancer Discov 5:1049-57, 2015
4. Drilon A, Laetsch TW, Kummar S, et al: Efficacy of Larotrectinib in TRK Fusion-Positive Cancers in Adults and Children. N Engl J Med 378:731-739, 2018
5. Drilon A, Siena S, Ou SI, et al: Safety and Antitumor Activity of the Multitargeted Pan-TRK, ROS1, and ALK Inhibitor Entrectinib: Combined Results from Two Phase I Trials (ALKA-372-001 and STARTRK-1). Cancer Discov 7:400-409, 2017
6. Couts KL, McCoach CE, Murphy D, et al: Acral Lentiginous Melanoma Harboring a ROS1 Gene Fusion With Clinical Response to Entrectinib. JCO Precision Oncology:1-7, 2017
7. Lovly CM, Gupta A, Lipson D, et al: Inflammatory myofibroblastic tumors harbor multiple potentially actionable kinase fusions. Cancer Discov 4:889-95, 2014
8. Subbiah V, Gainor JF, Rahal R, et al: Precision Targeted Therapy with BLU-667 for RET-Driven Cancers. Cancer Discov 8:836-849, 2018
9. Fernandez-Cuesta L, Plenker D, Osada H, et al: CD74-NRG1 fusions in lung adenocarcinoma. Cancer Discov 4:415-22, 2014
10. Jonna S, Feldman RA, Swensen J, et al: Detection of NRG1 Gene Fusions in Solid Tumors. Clin Cancer Res, 2019
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PL01.02 - The Evolution of Tissue Testing for Immunotherapy - Where Next? (Now Available) (ID 3581)
08:15 - 09:45 | Presenting Author(s): Keith Kerr
- Abstract
- Presentation
Abstract
Biomarkers have, to date, had an uneasy relationship with immunotherapy in lung cancer, a conflict between the degree of biomarker expression (largely PD-L1) being related to treatment efficacy, and a desire to give these drugs to everyone, either as monotherapy or, increasingly, in combination with other drugs. PD-L1 immunohistochemistry (IHC) is well established as a companion or complementary diagnostic, depending on indication, and tumour mutational burden (TMB) is an item of interest, with a surrogate, MSI-high, approved by the FDA in a tumour-type agnostic setting for second/greater line therapy.
Where is PD-L1 testing going?
PD-L1 IHC will remain a useful test. PD-L1 IHC scoring in cytology-type samples has been validated outside clinical trials and will become accepted in daily practice. New IHC clones will challenge the place of existing ones, hopefully validated by comparative study and EQA. Data are emerging on the clinical validity of PD-L1 scoring on small amounts of tumour (the heterogeneity issue), how few cells can be used, and the clinical impact of scoring PD-L1 on insufficient material.
Tumour Mutational Burden
Difficulties with the PD-L1 IHC biomarker drove the search for alternatives and TMB, as a several times removed surrogate of tumour immunogenicity, emerged. The place for TMB in the diagnostic algorithm remains uncertain but clinical trials looking at tumour tissue or blood TMB continue to provide promising, if confusing, results. Many of the issues with PD-L1 IHC are also in play with TMB. There is no consensus about what is ‘high TMB’? TMB is another biological continuum, like PD-L1 expression, so the creation of a binary high vs low categorization potentially ignores relative biological significance of different levels. There is huge variability in the methodology used to derive or predict TMB, the amount of the genome screened, different definitions of a ‘mutation’, different next generation sequencing platforms, different contexts (tumour tissue vs blood) and a lack of published data on how these different TMB assessment approaches vary. Anecdotal reports so far indicate substantial variation.
As a predictive biomarker in this setting, TMB works; it enriches a treatment group for benefit. But we have seen relatively little comparative data to suggest superiority over any other singular biomarker in this treatment area. TMB is a crude predictor of tumour neo-antigenicity and perhaps we should look to more specific measures of this aspect of sensitivity to immunotherapy. It is possible to predict probable neo-antigenicity from deep analysis of sequencing data. Neo-antigens should be clonal, rather than subclonal, to maximize their immune impact. Are their particular genes whose alteration would predict greater (or lesser) tumour ‘visbility’ to the immune system, be they involved in DNA repair, maintaining genome stability or integrity, antigen processing and presentation, or more likely to generate immunogenic proteins? Other factors such as loss of heterozygosity at MHC coding genes may also provide useful information.
So, it may well be possible to refine our assessment of TMB into a more specific and meaningful metric. This then raises the question of whether it is practical to do so, and whether this provides clinically useful information.
Tumour inflammation
For immune checkpoint inhibitors (ICI) to work, a tumour specific immune response must be ‘available’ and somehow inhibited by the checkpoints being therapeutically targeted. Assessments of tumour inflammation, as a presumptive sign of such an available but inhibited immune response, have been successfully used to enrich a treatment group for benefit from ICI therapy. In lung cancer, these assessments of inflammation have been relatively complex assays of immune gene signature expression using mRNA extracted for fresh/frozen tumour tissue. Initially large panels of immune response-related genes have been reduced to single digit-sized panels. Interferon gamma seems to be important as is, unsurprisingly, PD-L1.
The same questions arise with respect to immune gene signatures. Is this any better than a more simplistic approach such as PD-L1 IHC? Evidence is at best marginal, that it would be superior. Is this practical and affordable in a daily practice setting? Probably not. Are there alternative ways to derive the same information? Probably yes. In other tumour sites, a morphological assessment of tumour inflammation has been more keenly pursued than in lung cancer. This approach has tended to focus on the presence and location of the immune cell infiltrate and to some extent, on the nature of the infiltrating cells. When tumour sample area allows, immune cell activity at the tumour-stromal interface, and the presence of CD8-expressing T cells have been associated with better responses to ICI. There is much more that could be investigated, especially in relation to other immune-active or immune-suppressive cell types and their location within the tumour and its microenvironment (TME). Immunohistochemistry is readily available, but in order to understand the complexity of this process and find new biomarkers, in limited tissue samples, multiplex IHC and digital pathology analysis tools will almost certainly be required. These tools already exist but the challenge will be generating the data in relation to clinical response and then deployment in daily practice.
Other regulation in the TME
Other factors in the TME, such as tissue hypoxia and lactate dehydrogenase, are relevant biomarkers, indicating an immune-suppressive environment, and potential resistance to ICI therapy. Other factors like IDO, and other immune checkpoints like LAG3 and TIM3 may also confer resistance to current ICI therapy and provide new therapeutic targets.
Conclusion
There is much more to be learned about factors that regulate responsiveness to ICI therapy. The multifactorial complexity of the immune response suggests that combinations of biomarkers are more likely to provide better prediction of therapeutic benefit. Many of these factors are more likely to be continuous variables rather than binary metrics, and oncology will have to learn to deal with this situation, perhaps more akin to a complementary rather than a companion diagnostic, leading to more nuanced therapeutic decisions. It remains to be seen whether oncology, regulatory authorities or industry has an appetite for such an approach.
References
Blank CU et al. Science 2016;352,658
Camidge DR et al. Nat Rev Clin Oncol 2019;16,341
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PL01.03 - Will the Immunotherapy with Newer Biomarkers, Combination Therapy or New Technology Eventually Cure Lung Cancer? (Now Available) (ID 3582)
08:15 - 09:45 | Presenting Author(s): Tetsuya Mitsudomi
- Abstract
- Presentation
Abstract
The recent introduction of immune checkpoint therapy has greatly changed the clinical practice of non-small cell lung cancer (NSCLC). A battery of clinical trials showed the superiority of either PD-1 antibody monotherapy or PD-1/L1 antibody combined with chemotherapy as a first-line treatment of NSCLC over standard platinum doublet chemotherapy that has long been a standard of care. Hence, most if not all of NSCLC patients receive PD-1/L1 antibodies unless contraindicated due to coexisting immune-related comorbidities.
The recent update of the Keynote-001 trial showed that 5-year survival of the high expressors of PD-L1 treated with pembrolizumab as a first-line treatment was 23%. Especially, the 5-year survival rate of patients who received the first-line pembrolizumab more than 2 years was 79%. This really indicates that at least some of the NSCLC patients may be cured by monotherapy of PD-1 antibodies.
Conversely, about three fourth of patients, even with high expression of PD-L1 cannot survive for more than 5 years. This is natural considering the complexity of immunologic mechanisms against cancer. To be eliminated effectively by PD-1/L1 treatment, cancers should express their unique antigens typically generated by somatic mutations in the context of MHC. Therefore, the adequate quantity as well as the adequate quality of somatic mutations and intact antigen presentation, are prerequisite for immune response. When abnormal peptide is recognized by immune cells, adaptive expression of PD-L1 on the tumor cells occurs by secretion of interferon γ by T cells as a negative feedback that dampens antitumor immunity, Upon binding of PD-L1 with PD-1 on T cells downregulates T cell function. This tumor microenvironment (TME) is the best candidate for anti-PD-1/PD-L1 therapy. However, not all cancer has this TME. Besides PD-1/L1 systems, there are many other molecules such as CTLA4, TIGIT, TIM3, LAG3, etc. that negatively regulate the immune response. Regulatory T cells and myeloid-derived suppressor cells (MDSC) are also major players of immunosuppressive TME
To overcome these immunologic evasions, many strategies are being extensively sought. To enhance immune recognition of mutations and to prime new response, polypeptide or RNA-based vaccines that contain mutation-derived epitopes are being tested. For tumor cells that lost HLA molecules, enhancement of NK cell activities through NKG2A antibody or anti KIR antibody may be effective. To overcome adaptive immune resistance by molecules other that PD-1, use of blocking antibodies against above-mentioned other co-inhibitory molecules or agonistic antibodies against co-stimulatory molecules such as ICOS, GITR, 4-1BB, OX40, etc. is a rational way. Finally, to reverse immune suppressive TME, use of antibodies against CSF-1R and CCR4 to suppress MDSC and regulatory T cells, respectively, may be effective. Antagonists for immunosuppressive molecules such as adenosine A2AR, IDO, TGFb, etc are also expected to enhance tumor immunity.
Will the Immunotherapy eventually cure lung cancer? Currently, I have to say "Yes, for some but not sure for every patient". In this talk, I would like to discuss ongoing efforts to further improve outcomes of immune-therapy of lung cancer and future perspectives.
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PL01.04 - Artificial Intelligence, Big Data and Lung Cancer: Ready to Implement? (Now Available) (ID 3583)
08:15 - 09:45 | Presenting Author(s): Hugo Aerts
- Abstract
- Presentation
Abstract
A critical barrier present in cancer research and treatment today is when and how to act based on the information provided from tumor data. One important reason for the slow progress in the fight against cancer, is the fact that cancer is a “moving target”. It is constantly evolving and diversifying, changing its phenotype, its genomic composition, and through metastatic spread, even its location. This is even more true when subjected to the pressure of therapeutic intervention, where cancer evolution rapidly explores and exploits resistance mechanisms, potentially even aided by the mutagenic nature of cancer treatments, leaving the treating oncologist chasing a constantly changing disease.
Artificial Intelligence (AI) and Deep Learning technologies have recently led to revolutionary advances in areas ranging from computer vision to speech recognition - tasks that up to a few years ago could only be done by humans. AI has the potential to fundamentally alter the way medicine is practiced, as it excels in recognizing complex patterns in medical data and provides a quantitative, rather than qualitative, assessment of clinical conditions. AI-powered radiographic-biomarkers (“radiomics”) may quantify non-invasive information of the cancer phenotype that is clinically actionable, and may further improve diagnosis, characterization, and longitudinal tracking through therapy. AI methods are precise and allow specific quantification of features not otherwise quantifiable by human experts. Radiomic-analysis is performed on the entire tumor as compared to just a small sample for molecular analysis and provides a non-invasive window into internal growth pattern of the tumor (including internal textural heterogeneity, macroscopic necrosis, and viable tumor mass). Radiomics can thus quantify the phenotypic state of a tumor within its evolutionary process, thereby sidestepping issues relating to biopsies.
This is particularly important for patients with cancer, where different cancer lesions can express different microenvironments that could ultimately lead to heterogeneous response patterns. Despite the remarkable success of novel cancer therapies, the clinical benefit remains limited to a subset. Cancer therapies are often expensive and could bring unnecessary toxicity, there is a direct need to identify beneficial patients, but this remains difficult in the clinic today. Radiomics biomarkers could provide this information on a lesion and patient level using standard-of-care CT scans. Unlike biopsy assays that - by definition - only represent a sample within the tumor, imaging can depict a full picture of the entire tumor burden, providing information of each cancer lesion within a single non-invasive examination.
Another field that will be impacted by AI and big data is radiation oncology. Radiation oncology as a therapeutic specialty presents itself as an exemplary field that will be impacted by AI automation. Especially as much of the current radiation therapy work flow requires time-consuming, manual labor by both radiation oncologists and a team of medical staff including medical physicists, certified medical dosimetrists, and radiation therapists. The growing complexity of the human-machine and human-software interactions in conjunction with the increasing incidences of cancer have created a workforce shortage throughout the world. In fact, variations in the radiation treatment planning process can lead to significant differences in the quality of care, and negatively impact overall survival even in clinical settings where extra care is given to standardizing segmentation and planning approaches. Furthermore, the knowledge and experience gap between more developed and under-resourced health care environments poses an enormous public health challenge and represents one of the great global inequities in cancer care.
In this talk, Dr. Aerts will discuss recent developments from his group and collaborators performing research at the intersection of artificial intelligence big data, and oncology. Also, he will discuss recent work of building a computational image analysis system to extract deep learning algorithms and use these to build radiomic signatures. The presentation will conclude with a discussion of future work on building integrative systems incorporating both molecular and phenotypic data to improve cancer therapies.
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PL02 - Presidential Symposium including Top 7 Rated Abstracts (ID 89)
- Event: WCLC 2019
- Type: Plenary Session
- Track:
- Presentations: 11
- Now Available
- Moderators:Giorgio Vittorio Scagliotti, Ramon Rami-Porta
- Coordinates: 9/09/2019, 08:00 - 10:15, Barcelona (2005)
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PL02.02 - Lung Cancer Screenee Selection by USPSTF Versus PLCOm2012 Criteria – Interim ILST Findings (Now Available) (ID 2804)
08:00 - 10:15 | Presenting Author(s): Stephen Lam | Author(s): Renelle Myers, Mamta Ruparel, Sukhinder Kaur Atkar-Khattra, Emily Stone, Renne Manser, Annette Maree McWilliams, Paul Fogarty, David CL Lam, John Yee, John Mayo, Christine Dorothy Berg, Sam Janes, Kwun M Fong, Martin Tammemagi
- Abstract
- Presentation
Background
The National Lung Screening Trial showed that lung cancer screening of high-risk individuals with low dose computed tomography can reduce lung cancer mortality by 20%. Critically important is enrolling high-risk individuals. Most current guidelines including the United States Preventive Services Task Force (USPSTF) and Center for Medicare and Medicaid Services (CMS) recommend screening using variants of the NLST eligibility criteria: smoking ≥30 pack-years, smoking within 15 years, and age 55-80 and 55-77 years. Many studies indicate that using accurate risk prediction models is superior for selecting individuals for screening, but these findings are based on retrospective analyses. The International Lung Screen Trial (ILST) was implemented to prospectively identify which approach is superior.
Method
ILST is a multi-centred trial enrolling 4000 participants. Individuals will be offered screening if they are USPSTF criteria positive or have PLCOm2012 model 6-year risk ≥1.5%. Participants will receive two annual screens and will be followed for six years for lung cancer outcomes. Individuals not qualifying by either criteria will not be offered screening, but samples of them will be followed for lung cancer outcomes. Outcomes in discordant groups, USPSTF+ve/PLCOm2012-ve and PLCOm2012+ve/USPSTF-ve, are informative. Numbers of lung cancers and individuals enrolled, sensitivity, specificity and positive predictive values (PPV) of the two criteria will be compared.
Result
As of March 2019, ILST centers in Canada (British Columbia), Australia, Hong Kong, and the United Kingdom had enrolled and scanned 3673 individuals. Study results are summarized in Figure 1.
Conclusion
Interim analysis of ILST data, indicates that classification accuracy of lung cancer screening outcomes support the PLCOm2012 criteria over the USPSTF criteria. The PLCOm2012 criteria detected significantly more lung cancers. Individuals who are USPSTF+ve and PLCOm2012-ve appear to be at such low baseline risk (0.2%) that they may be unlikely to benefit from screening.
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PL02.03 - Early Detection of Cancer of the Lung Scotland (ECLS): Trial Results (Now Available) (ID 557)
08:00 - 10:15 | Presenting Author(s): Frank Sullivan | Author(s): Stuart Schembri
- Abstract
- Presentation
Background
Scotland has one of the highest rates of lung cancer in the world -- 460 men and 340 women in 100 000 are diagnosed with lung cancer every year. In the UK, survival from lung cancer is poor with less than 9% of patients still alive at five years after diagnosis, due primarily to the late stage of presentation. The EarlyCDT®-Lung Test is a novel Autoantibody(AAB) diagnostic test for the early detection of lung cancer allowing stratification of individuals according to their risk of developing lung cancer. The Test measures seven AABs; p53, NYESO-1, CAGE, GBU4-5, HuD, MAGE A4 & SOX2. It identifies 41% of lung cancers with a high specificity of 90%. This compares to CT scanning, which when used
Method
alone as a prevalence screening test, identifies 67% of lung cancers developing over the following 12 months, but has a low specificity of around 49%. The autoantibodies detected in the test have not been shown to vary with age, gender and ethnicity. The primary research question is: ‘Does using the EarlyCDT®-Lung Test, followed by X-ray and CT scanning, to identify those at high risk of lung cancer reduce the incidence of patients with late-stage lung cancer (III & IV) or unclassified presentation (U) at diagnosis, compared to standard clinical practice?’
An RCT in 12,208 participants
Participants
Asymptomatic adults aged 50 to 75 who had a high risk of developing lung cancer over the next 24 months were eligible to participate. 5 290/12 209 (43.3%) of the subjects lived in the most deprived quintile with the mean age at recruitment 60.5 years and the mean pack years smoked 38.2 . Participants were allocated to intervention or comparison group during the recruitment visit using a web-based randomization system. Test positive patients were offered a chest X-ray followed by a non-contrast thoracic CT scan. If the initial CT scan revealed no evidence of lung cancer then subsequent CT scans were offered 6 monthly for 24 months. Individuals with abnormalities were followed up over the study period or referred for clinical care as appropriate. All individuals entering the study were followed up via record linkage including the Scottish Cancer Registry.Control
UK standard clinical practice
OUTCOMES
Primary
The difference, at 24 months after randomisation, between the rates of patients with stage III, IV or unclassified lung cancer at diagnosis in the intervention arm & control arm;
Secondary
Eight further measures including mortality, economic and psychological.
Power
Using an assumption of 600/100,000 for late stage lung cancer in the population studied and acknowledging that recruitment is over a 2 year period the study has a power of 80% to detect a 35% reduction associated with the use of the EarlyCDT-Lung test to identify cases.Analysis
Result
Cox proportional hazards models were used to estimate the hazard ratio of the rate of late stage lung cancer in the intervention arm compared to the control arm. Participants who were lost to follow up were censored. The models adjust for age, gender, smoking history, and practice. Random cluster effects were included rather than fixed effects for practices. Comparisons of proportions were carried out using chi square tests. Fisher’s Exact test was used if the numbers of events are small.
127 lung cancers were diagnosed in the study period (56 in the intervention group and 71 in the control arm). 9.8% of the intervention group had a positive EarlyCDT-Lung test and 3.4% (n=18) of these were diagnosed with lung cancer in the study period.
Conclusion
Fewer participants in the intervention group were diagnosed at a late-stage (III & IV) compared with the control group (33 vs 52). The rate of late-stage (III & IV) lung cancer diagnosis in the intervention group was 58.9% and in the control group was 73.2%. The number of early-stage (I & II) lung cancers diagnosed in the intervention group was higher than in the control group (23 vs 19). The EarlyCDT-Lung test was positive for 12 of
the 23 early cancers (sensitivity 52.2%, 95% CI 30.6% to 73.2%) and for 6 of the 33 late-stage cancers (sensitivity 18.2%, 95% CI 7.2% to 35.5%).
The study was not powered to detect a difference in mortality, however there was a non significant trend suggesting fewer deaths in the intervention arm compared to the control (87 vs 108 respectively). Similar results were noted relating to lung cancer-specific mortality (17 vs 24).
Our results show that the combination of the EarlyCDT-Lung followed by CT imaging in those with a positive blood test, results in a significant decrease in late stage diagnosis of lung cancer and may decrease all cause and lung cancer specific mortality. We shall continue follow up of all participants’ lung cancer and mortality outcomes at 5 years using Scottish ISD (Information Services Division) data to study these effects further.
Blood-based biomarker panels, such as the EarlyCDT-Lung test, may have an important role in future lung cancer screening programmes. Further studies including ones to establish the ideal testing frequency are required.Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
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PL02.04 - Blood MicroRNA and LDCT Reduce Unnecessary LDCT Repeats in Lung Cancer Screening: Results of Prospective BioMILD Trial (Now Available) (ID 907)
08:00 - 10:15 | Presenting Author(s): Ugo Pastorino | Author(s): Mattia Boeri, Stefano Sestini, Federica Sabia, Mario Silva, Paola Suatoni, Carla Verri, Anna Cantarutti, Nicola Sverzellati, Giovanni Corrao, Alfonso Marchianò, Gabriella Sozzi
- Abstract
- Presentation
Background
The National Lung Screening Trial (NLST) showed that lung cancer (LC) screening by three annual rounds of low-dose computed tomography (LDCT) reduced lung cancer mortality, and MILD trial provided additional evidence that extended intervention beyond 5 years, with annual or biennial rounds, enhanced the benefit of screening. The new bioMILD trial tested the additional value of blood microRNA (miRNA) assay at the time of LDCT on a large series of volunteers, with the aim of targeting next LDCT intervals on the basis of individual risk profile.
Method
BioMILD trial offered a lung cancer screening program combining LDCT and blood microRNA assay, to heavy smokers (current or former ≤10 years) aged 50-75 years (clinicaltrials.gov ID: NCT02247453). At baseline, LDCT and miRNA were tested independently with blind evaluation, choosing a 3-year interval for the next repeat in participants with double negative LDCT and miRNA.
Result
From January 2013 to March 2016, bioMILD prospectively enrolled 4,119 volunteers at Istituto Nazionale Tumori of Milan. The median age was 60 years, median pack-years 42, current smokers 79% and females 39%. According to baseline LDCT and miRNA profile, 2384 subjects (58%) with double negative LDCT and miRNA (2neg) were sent to 3-year LDCT repeat, 1526 (37%) with positive miRNA or indeterminate/positive LDCT (1pos) and 209 (5%) with positive miRNA and indeterminate/positive LDCT (2pos) were sent to annual or shorter LDCT repeat, depending on LDCT results. After four screening runs (LDCT 0/1/2/3), a total of 115 LCs were diagnosed (2.8%). Cumulative LC incidence was significantly different in the three groups: 0.6% for 2neg subjects, 3.8% for 1pos and 20.1% for 2pos (p<0.0001); LC mortality was 0.1%, 0.6% and 3.8% respectively (p<0.0001). Interval cancer incidence, proportion of stage I and resected LC were not statistically different among groups.
Conclusion
The combination of microRNA assay and LDCT is a valuable and safe tool to assess individual risk profile and reduce unnecessary LDCT repeats in lung cancer screening. Targeting LDCT intervals on individual risk profile did not cause any detrimental effects on LC detection or mortality.
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PL02.05 - Discussant - PL02.02, PL02.03, PL02.04 (Now Available) (ID 3912)
08:00 - 10:15 | Presenting Author(s): Harry J. de Koning
- Abstract
- Presentation
Abstract not provided
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PL02.06 - In Hospital Clinical Efficacy, Safety and Oncologic Outcomes from VIOLET: A UK Multi-Centre RCT of VATS Versus Open Lobectomy for Lung Cancer (Now Available) (ID 1257)
08:00 - 10:15 | Presenting Author(s): Eric Lim | Author(s): Tim Batchelor, Joel Dunning, Michael Shackcloth, Vladimir Anikin, Babu Naidu, Elizabeth Belcher, Mahmoud Loubani, Vipin Zamvar, Tim Brush, Lucy Dabner, Rosie Harris, Dawn Phillips, Chloe Beard, Holly McKeon, Sangeetha Paramasivan, Daisy Elliott, Alba Realpe Rojas, Elizabeth Stokes, Sarah Wordsworth, Jane Blazeby, Chris Rogers, T Violet Trialists
- Abstract
- Presentation
Background
VATS is currently the most popular form of access for lung cancer resection in the UK. However, there is limited comparative information from high quality randomised controlled trials and no information on early oncologic outcomes for quality assurance for a minimal access approach. VIOLET is the largest randomised trial conducted to date to compare clinical efficacy, safety and oncologic outcomes of VATS versus open surgery for lung cancer.
Method
VIOLET is a parallel group randomised trial conducted across 9 UK thoracic surgery centres. Participants with known or suspected primary lung cancer were randomised in a 1:1 ratio to VATS (one to four ports) or open lobectomy. Randomisation was stratified by surgeon. Patients within clinical stage cT1-3, N0-1 and M0 using TNM 8 with disease suitable for VATS or open surgery were eligible to join the trial. We report on early outcomes in the period from randomisation to hospital discharge after surgery.
Result
From Jul 2015 to Feb 2019, 2,109 patients were screened to randomise 503 participants to VATS (n=247) or open (n=256) lobectomy. The mean age (SD) was 69 (8.8) years and 249 (49.5%) were male. Baseline clinical T category was cT1 333 (67.3%), cT2 125 (25.2%), cT3 37 (7.5%) with cN0 466 (94%) and cN1 30 (6%). Lobectomy was undertaken in 221 (89.5%) patients randomised to VATS and 232 (90.6%) patients randomised to open surgery. The in-hospital mortality rate was 1.4% (7/502) and the conversion rate from VATS to open was 5.7% (14/246) with the main reasons listed as pleural adhesions (n=4) and bleeding (n=4).
There were no differences in R0 resection; which was 98.8% (218/223) in the VATS group and 97.4% (228/234) in the open group; P=0.839 or in nodal upstaging from cN0/1 to pN2 disease which was observed in 6.2% (15/244) of the VATS group and 4.8% (12/252) of the open group; P=0.503.
The median (visual analogue) pain score was 4 (interquartile range, IQR 2 to 5) in both groups on day one with 3 (1 to 5) in the VATS group and 4 (2 to 5) in the open group on day two.
A significant reduction of overall in-hospital complications was observed in patients receiving VATS at 32.8% (81/247) compared to open 44.3% (113/255) surgery; P=0.008 without any difference in serious adverse events between the two groups, which was 8.1% (20/247) for VATS and 7.8% (20/255) for open surgery; P=0.897.
Patients randomised to VATS had a shorter median (IQR) length of stay of 4 (3 to 7) versus 5 (3 to 8) days compared to patients randomised to open surgery, P=0.008.
Conclusion
In early stage lung cancer, VATS lobectomy is associated with significantly lower in-hospital complications and shorter length of stay compared to open lobectomy. This was achieved without any compromise to early oncologic outcomes (pathologic complete resection and upstaging of mediastinal lymph nodes) nor any difference in serious adverse events in the early post-operative period.
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PL02.07 - Discussant - PL02.06 (Now Available) (ID 3913)
08:00 - 10:15 | Presenting Author(s): Jessica S Donington
- Abstract
- Presentation
Abstract not provided
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PL02.08 - Registrational Results of LIBRETTO-001: A Phase 1/2 Trial of LOXO-292 in Patients with RET Fusion-Positive Lung Cancers (Now Available) (ID 964)
08:00 - 10:15 | Presenting Author(s): Alexander Drilon | Author(s): Geoffrey R Oxnard, Lori Wirth, Benjamin Besse, Oliver Gautschi, Shao Weng Daniel Tan, Herbert H. Loong, Todd Bauer, Yu Jung Kim, Atsushi Horiike, Keunchil Park, Manisha Shah, Caroline McCoach, Lyudmila Bazhenova, Takashi Seto, Marcia Brose, Nathan Pennell, Jared Weiss, Ignacio Matos, Nir Peled, Byoung Chul Cho, Yuichiro Ohe, Karen L Reckamp, Valentina Boni, Miyako Satouchi, Gerald S Falchook, Wallace Akerley, Haruko Daga, Tomohiro Sakamoto, Jyoti D Patel, Nehal Lakhani, Fabrice Barlesi, Mark Burkard, Viola W. Zhu, Victor Moreno, Jacques Medioni, Marc Matrana, Christian Rolfo, Dae Ho Lee, Hovav Nechushtan, Melissa Johnson, Vamsidhar Velcheti, Makoto Nishio, Ryo Toyozawa, Kadoaki Ohashi, Lucy Song, Ji-Youn Han, Alexander Spira, Filippo Guglielmo Maria De Braud, Kristoffer Staal Rohrberg, Shinji Takeuchi, Jun Sakakibara-Konishi, Saiama Waqar, Hirotsugu Kenmotsu, Frederick Wilson, Binoj Nair, Elizabeth Olek, Jennifer Kherani, Kevin Ebata, Edward Zhu, Michele Nguyen, Luxi Yang, Xin Huang, Scott Cruickshank, Stephen Michael Rothenberg, Benjamin J Solomon, Koichi Goto, Vivek Subbiah
- Abstract
- Presentation
Background
No targeted therapy is currently approved for patients with RET fusion-positive non-small cell lung cancer (NSCLC). LOXO-292 is a highly selective RET inhibitor with activity against diverse RET fusions, activating RET mutations and brain metastases. Based on initial data from LIBRETTO-001, LOXO-292 received FDA Breakthrough Designation for the treatment of RET fusion-positive NSCLC in August 2018.
Method
This global phase 1/2 study (87 sites, 16 countries) enrolled patients with advanced RET-altered solid tumors including RET fusion-positive NSCLC (NCT03157128). LOXO-292 was dosed orally in 28-day cycles. The phase 1 portion established the MTD/RP2D (160 mg BID). The phase 2 portion enrolled patients to one of six cohorts based on tumor type, RET alteration, and prior therapies. The primary endpoint was ORR (RECIST 1.1). Secondary endpoints included DoR, CNS ORR, CNS DoR, PFS, OS, safety and PK.
Result
As of 17-June 2019, 253 RET fusion-positive NSCLC patients were treated. The primary analysis set (PAS) for LOXO-292 registration, as defined with the US FDA, consists of the first 105 consecutively enrolled RET fusion-positive NSCLC patients who received prior platinum-based chemotherapy; 58 patients (55%) also received prior anti PD-1/PD-L1 agents. The majority of PAS responders have been followed for ≥6 months from first response. Of the remaining 148 patients, 79 had previously been treated with platinum-based chemotherapy, 55 did not receive prior platinum-based chemotherapy and 14 did not have measurable disease at baseline.
Conclusion
Among PAS patients, the investigator-assessed ORR was 68% (95% CI 58-76%, n=71/105, 2 PRs pending confirmation). Responses did not differ by fusion partner or the type or number of prior therapies, including chemotherapy, anti PD-1/PD-L1 agents and multikinase inhibitors with anti-RET activity. The median DoR was 20.3 months (95% CI 13.8-24.0) with a median follow-up of 8 months; as evidenced by the wide confidence interval, this DoR estimate is not statistically stable due to a low number of events (16 of 69 confirmed responders). The intracranial ORR was 91% (n=10/11: 2 confirmed CRs, 8 confirmed PRs) for patients with measurable brain metastases at baseline.
The ORR in efficacy evaluable treatment naïve RET fusion-positive NSCLC patients was 85% (95% CI 69-95%, n=29/34, 7 PRs pending confirmation). In the safety data set of all 531 patients, 5 treatment-related AEs occurred in ≥15% of patients: dry mouth, diarrhea, hypertension, increased AST and increased ALT. Most AEs were grade 1-2. Only 9 of 531 (1.7%) patients discontinued LOXO-292 for treatment-related AEs.
LOXO-292 had marked antitumor activity in RET fusion-positive NSCLC patients and was well tolerated. These data will form the basis of an FDA NDA submission later this year.
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PL02.09 - National Lung Matrix Trial (NLMT): First Results from an Umbrella Phase II Trial in Advanced Non-Small Cell Lung Cancer (NSCLC) (ID 2282)
08:00 - 10:15 | Presenting Author(s): Gary William Middleton | Author(s): Sanjay Popat, Peter Fletcher, Yvonne J. Summers, Alastair Greystoke, David Gilligan, Judith Cave, Noelle O'Rourke, Alison Brewster, Elizabeth W. Toy, James Spicer, Joshua Stephen Savage, Rowena Sharpe, Timothy A. Yap, Charles Swanton, Lucinda Billingham
- Abstract
Background
Oncogene-addicted NSCLC can achieve substantial clinical benefit with single-agent targeted therapy. Seeking to extend this paradigm to other more genetically complex NSCLC, we report first results of NLMT, an umbrella phase II trial whereby a bespoke next-generation sequencing screening panel (Stratified Medicine Programme 2) stratifies NSCLC patients to rationally selected targeted therapies. Uniquely we present results across the entirety of the platform to enable an assessment of the potential to further stratify medicine in advanced NSCLC. Novel methodology is used to ensure that the integrity of this ongoing platform trial is not jeopardised.
Method
NLMT uses a Bayesian adaptive design to screen currently 8 targeted drugs for signals of activity in 22 molecularly defined cohorts. For single agents, pre-specified clinically relevant outcomes are either median progression-free survival (mPFS) >3 months or objective response rate (ORR) and/or durable clinical benefit rate at 24 weeks (DCBR) >30%. Target recruitment for each cohort is 30 with futility analyses at 15. Recruitment continues in 19 cohorts. We report posterior probabilities (PP) of a clinically relevant outcome for closed cohorts and Bayesian predictive probability of success (PPoS) given observed data for open cohorts. This novel approach provides insight into the drug-biomarker combinations that have the strongest potential for further research.
Result
Over a 4 year period to end of March 2019, NLMT has recruited 286 patients from >4000 screened. Of 6 palbociclib cohorts (all proficient Rb): mPFS in KRAS mutation (n=30) is 5.8 months (PP>0.99); CDKN2A loss/non-squamous (n=27) passed its interim analysis; we predict >75% PPoS, given current data, in CDKN2A loss/squamous (n=16) and CCND1 amplification (n=13). Data for crizotinib show >90% PPoS in ROS1 gene fusions (n=8) and MET exon 14 skipping mutation (n=8), with less clear signal for MET amplification (n=9). Responses to selumetinib/docetaxel in NF1 mutation (n=16) warrant continuation. Recruitment to vistusertib was halted at interim for LKB1 single mutation (ORR=0/15, PP=0.003; DCBR=1/15, PP=0.026), but DCBR in LKB1/KRAS double mutation (n=23) warrant continuation. 4 cohorts receive capivasertib (n=22): data in PIK3CA amplifications (n=9) indicate <15% PPoS.
Conclusion
These first results from the largest stratified medicine dataset in NSCLC indicate further molecular stratifications could benefit from targeted therapies. Reporting interim outputs for all cohorts will allow reappraisal of the global stratified medicine strategy in cancer.
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PL02.10 - Discussant - PL02.08, PL02.09 (Now Available) (ID 3914)
08:00 - 10:15 | Presenting Author(s): Robert C. Doebele
- Abstract
- Presentation
Abstract not provided
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PL02.11 - Overall Survival with Durvalumab Plus Etoposide-Platinum in First-Line Extensive-Stage SCLC: Results from the CASPIAN Study (Now Available) (ID 2265)
08:00 - 10:15 | Presenting Author(s): Luis Paz-Ares | Author(s): Yuanbin Chen, Niels Reinmuth, Katsuyuki Hotta, Dmytro Trukhin, Galina Statsenko, Maximilian J. Hochmair, Mustafa Özgüroğlu, Jun Ho Ji, Oleksandr Voitko, Artem Poltoratskiy, Santiago Ponce, Francesco Verderame, Libor Havel, Igor Bondarenko, Andrzej Kazarnowicz, György Losonczy, Nikolay V. Conev, Jon Armstrong, Natalie Byrne, Norah Shire, Haiyi Jiang, Jonathan Goldman
- Abstract
- Presentation
Background
Extensive-stage (ES)-SCLC is a recalcitrant disease associated with a median OS of ~10 months following etoposide-platinum (EP); new treatments that prolong survival are needed. CASPIAN (NCT03043872) is an open-label, phase 3 study of durvalumab (anti-PD-L1), ± tremelimumab (anti-CTLA-4), combined with EP as first-line treatment for patients with ES-SCLC. Here we report results for durvalumab + EP (D+EP) versus EP from a planned interim analysis.
Method
Patients with previously untreated ES-SCLC (ECOG PS 0/1) were randomised (1:1:1) to durvalumab 1500 mg + EP q3w; durvalumab 1500 mg + tremelimumab 75 mg + EP q3w; or EP q3w. Patients in immunotherapy arms received up to 4 cycles of EP followed by maintenance durvalumab until progression. Patients in the EP arm received up to 6 cycles of EP and prophylactic cranial irradiation (PCI), at the investigator’s discretion. Investigator’s choice of cisplatin or carboplatin was allowed across all arms and was a stratification factor at randomisation. The primary endpoint was OS. Data cutoff: 11 March 2019.
Result
268 patients were randomised to D+EP and 269 to EP. Baseline characteristics were well balanced between arms. In the EP arm, 56.8% of patients received 6 cycles of EP. At the interim analysis, D+EP significantly improved OS compared to EP with a HR of 0.73 (95% CI, 0.591-0.909; p=0.0047); mOS 13.0 versus 10.3 months, respectively. 33.9% of patients were alive at 18 months with D+EP versus 24.7% with EP. Secondary endpoints of PFS and ORR were also improved with D+EP compared to EP: PFS HR 0.78 (95% CI, 0.645-0.936); mPFS 5.1 versus 5.4 months; 12-month PFS rate 17.5% versus 4.7%; investigator-assessed ORR (RECIST v1.1; unconfirmed) 79.5% versus 70.3% (odds ratio, 1.64 [95% CI, 1.106-2.443]). The incidences of grade 3/4 AEs (61.5% versus 62.4%) and AEs leading to discontinuation (9.4% each) were similar between arms; the incidence of haematological toxicities was numerically higher in the EP arm. The durvalumab + tremelimumab + EP arm continues blinded to final analysis.
Conclusion
The addition of durvalumab to EP as first-line treatment for ES-SCLC significantly improved OS (27% reduction in risk of death) versus a robust control arm that permitted up to 6 cycles of EP and PCI. Of note, this chemo-immunotherapy regimen offers flexibility in platinum choice (carboplatin or cisplatin), reflecting current clinical practice for this challenging disease. No new safety signals were identified.
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PL02.12 - Discussant - PL02.11 (Now Available) (ID 3915)
08:00 - 10:15 | Presenting Author(s): Myung-Ju Ahn
- Abstract
- Presentation
Abstract not provided
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Author of
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IASLC General Assembly (ID 364)
- Event: WCLC 2019
- Type: General Assembly
- Track:
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/10/2019, 08:00 - 08:45, Tokyo (1982)
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GA01.01 - Welcome (Now Available) (ID 3909)
08:00 - 08:45 | Presenting Author(s): Giorgio Vittorio Scagliotti
- Abstract
- Presentation
Abstract not provided
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ES22 - Immunotherapy - Discovering New Areas (ID 25)
- Event: WCLC 2019
- Type: Educational Session
- Track: Immuno-oncology
- Presentations: 1
- Now Available
- Moderators:Manuel Cobo, Antonio Araujo
- Coordinates: 9/09/2019, 15:45 - 17:15, Vienna (2016)
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ES22.04 - Any Chance in Mesothelioma (Now Available) (ID 3278)
15:45 - 17:15 | Presenting Author(s): Giorgio Vittorio Scagliotti
- Abstract
- Presentation
Abstract
Section not applicable
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MA11 - Immunotherapy in Special Populations and Predictive Markers (ID 135)
- Event: WCLC 2019
- Type: Mini Oral Session
- Track: Immuno-oncology
- Presentations: 1
- Now Available
- Moderators:Frank Griesinger, Lecia Sequist
- Coordinates: 9/09/2019, 14:00 - 15:30, Hilton Head (1978)
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MA11.11 - STK11/LKB1 Genomic Alterations Are Associated with Inferior Clinical Outcomes with Chemo-Immunotherapy in Non-Squamous NSCLC (Now Available) (ID 2898)
14:00 - 15:30 | Author(s): Giorgio Vittorio Scagliotti
- Abstract
- Presentation
Background
Addition of pembrolizumab (P) to platinum-doublet chemotherapy [carboplatin (or cisplatin) and pemetrexed (CP)] prolongs overall survival and is a standard of care (SOC) for the 1st line treatment of metastatic EGFR/ALK wild-type (wt) non-squamous non-small cell lung cancer (mnsNSCLC). Despite widespread use of the CPP regimen, molecular determinants of clinical benefit from the addition of P to CP remain poorly defined. We previously identified genomic alterations in STK11/LKB1 as a major driver of primary resistance to PD-1/PD-L1 blockade in mnsNSCLC. Here, we present updated data on the impact of STK11/LKB1 alterations on clinical outcomes with CPP chemo-immunotherapy from a large retrospective multi-institution international study.
Method
620 pts with mnsNSCLC and tumor genomic profiling encompassing STK11/LKB1 from 21 academic institutions in the US and Europe were included in this study. Clinical outcomes were collected for two distinct patient cohorts: a) 468 pts treated with first-line CPP (or >1st line following FDA-approved TKIs) that were alive for 14 days thereafter and b) 152 STK11/LKB1-mt pts that received CP prior to regulatory approval of CPP.
Result
Among 468 CPP-treated pts, STK11/LKB1 genomic alterations (N=118) were associated with significantly shorter PFS (mPFS 5.0m vs 6.8m, HR 1.45, 95% CI 1.11 to 1.91; P=0.007) and shorter OS (mOS 10.6m vs 16.7m, HR 1.46, 95% CI 1.04 to 2.07; P=0.031) compared with STK11/LKB1-wt tumors (N=350). The likelihood of disease progression as BOR to CPP differed significantly between the two groups (29.5% vs 17%, P= 0.006). Similar results were obtained when limiting the analysis to EGFR and ALK-wt tumors (N=435) (mPFS 5.0m vs 6.9m, HR 1.48, 95% CI 1.12-1.95, P=0.006 and mOS 10.6m vs 16.7m, HR 1.45, 95% CI 1.02-2.05, P=0.036). Importantly, in pts with STK11/LKB1-mt mnsNSCLC, addition of pembrolizumab to CP did not result in significant improvement of PFS (mPFS 5.0m vs 3.9m, HR 0.82, 95% CI 0.63 to 1.07, P=0.14) or OS (mOS 10.6m vs 9.1m, HR 0.93, 95% CI 0.67 to 1.30, P=0.69) compared to CP alone.
Conclusion
In mnsNSCLC, STK11/LKB1 alterations define a subgroup of pts with inferior clinical outcomes with CPP and lack of benefit from the addition of pembrolizumab to CP chemotherapy. Novel therapeutic strategies are required to establish effective antitumor immunity in STK11/LKB1-mutant NSCLC.
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MA21 - Non EGFR/MET Targeted Therapies (ID 153)
- Event: WCLC 2019
- Type: Mini Oral Session
- Track: Targeted Therapy
- Presentations: 1
- Now Available
- Moderators:Benjamin Besse, Michael Thomas
- Coordinates: 9/10/2019, 14:30 - 16:00, Vienna (2016)
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MA21.03 - The International Association for the Study of Lung Cancer (IASLC) Global Survey on Molecular Testing in Lung Cancer (Now Available) (ID 1198)
14:30 - 16:00 | Author(s): Giorgio Vittorio Scagliotti
- Abstract
- Presentation
Background
Evidence-based standards for molecular testing of lung cancer have been established, but the global frequency and practice of testing are not well understood. The IASLC conducted an international survey to evaluate current practice and barriers to molecular testing.
Method
Distributed to IASLC members and other healthcare professionals, content included: 7-question introduction, 32 questions for those requesting tests/treating patients, 45 questions on performing/interpreting assays, and 24 questions on tissue acquisition. All respondents were asked to provide 3-5 barriers to implementing/offering molecular testing.
Respondents’ countries were grouped by geography or developing/developed using IASLC and World Bank criteria. Surveys were available in 7 languages. Regional comparisons used the Chi-squared test or ANOVA; free-text was analyzed with Nvivo.
Result
We obtained 2,537 responses from 102 countries. Respondents were 45% Medical Oncologists, 12% Pulmonologists, 12% Thoracic Surgeons, 9% Pathologists, and 22% scientists or other. 56% of responses were from developing countries, 44% developed. Regions included: 52% Asia, 19% Europe, 11% Latin America, 11% US/Canada, 7% Other.
1683 (66%) chose the requesting/treating track (50% government, 42% academic, 8% other). 61% reported most patients in their country do not receive molecular testing, with the lowest rates in Latin America/Other (p<0.0001). 39% were not satisfied with the conditions of molecular testing in their country. Indications for requesting testing included: adenocarcinoma (89%), never-smoker (61%), female (57%), and young (54%) (variable by region, p<0.0001). 99% ordered EGFR, 95% ALK, 84% PDL1, 79% ROS1, all other tests <50%. 56% typically received results within 10 days. Only 67% were aware of CAP/IASLC/AMP guidelines, least frequently in Asia/Other (p=0.041). 37% have trouble understanding molecular testing result reports, most of whom cited a need for more technical and scientific knowledge. 75% had multidisciplinary tumor boards, but 23% met <1/month.
The 316 (12%) testing track respondents were from laboratories that were 49% academic, 35% government, and 16% private/other. 94% of laboratories offered EGFR, 83% ALK, 69% KRAS, 68% BRAF, 64% ROS1, 56% HER2, and others <50%; 68% tested for PDL1. 57% offered Multiplex assays, less frequently in Latin America/Asia (p=0.0294). 69% tested blood-derived DNA, less frequently in US/Canada/Other (0.0013). 23% of respondents reported >10% of cases are rejected due to inadequate samples; however, 47% stated there is no policy or strategy to improve the quality of the tissue samples in their country. 52% reported patients/physicians are not satisfied with the state of molecular testing in their country. Respondents performing/interpreting assays (334, 14%) were typically informed of biopsy results (91%), and notified when the sample was inadequate (84%).
The most frequent barrier to molecular testing in every region was cost, followed by quality/standards, turnaround-time, access, and awareness. After cost, time was the most common barrier in developed countries, while it was quality in developing countries. The second largest barrier was quality in Asia, access in Europe/Latin America/Other, and turn-around time in US/Canada.
Conclusion
These preliminary analyses show molecular testing usage varies across the globe. Barriers vary by region, and one-third of respondents were unaware of evidence-based guidelines. Global and regional strategies should be developed to address barriers.
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OA07 - Precision Medicine Involves Biology and Patients (ID 132)
- Event: WCLC 2019
- Type: Oral Session
- Track: Advanced NSCLC
- Presentations: 1
- Now Available
- Moderators:Silvia Novello, Fabrice Barlesi
- Coordinates: 9/09/2019, 11:00 - 12:30, Copenhagen (1980)
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OA07.07 - Quality of Life (QoL) Analysis in Lung Cancer: A Systematic Review of Phase III Trials Published Between 2012 and 2018 (Now Available) (ID 1958)
11:00 - 12:30 | Author(s): Giorgio Vittorio Scagliotti
- Abstract
- Presentation
Background
We previously reported that QoL is not included among endpoints and QoL results are underreported in a high proportion of phase III trials in oncology. Here we describe QoL prevalence and heterogeneity in QoL reporting in lung cancer phase III trials.
Method
We selected all primary publications of lung cancer phase III trials evaluating anticancer drugs published between 2012 and 2018 by 11 major journals. We analyzed QoL inclusion among endpoints, presence of QoL results and methodology of QoL analysis.
Result
122 publications were identified. In 39 (32.0%) publications, QoL was not listed among endpoints: 10/17 (58.8%) early stage/locally advanced NSCLC, 15/54 (27.8%) first-line of advanced NSCLC; 10/41 (24.4%) second and further lines of advanced NSCLC, 4/10 (40.0%) SCLC. Proportion of trials not including QoL was similar over time: 32.9% publications in 2012-2015 vs. 30.6% in 2016-2018. QoL was not listed among endpoints in primary publication in 16/80 (20.0%) for-profit trials vs. 23/42 (54.8%) no-profit trials. Out of 83 trials including QoL among endpoints, QoL results were not reported in 36 primary publications (43.4%). Proportion of trials not reporting QoL results in primary publication significantly increased over time (30.6% 2012-2015 vs. 61.8% 2016-2018, p=0.005). Overall, QoL data were not available in 65/122 (61.5%) primary publications, due to the absence as endpoint or unpublished results. QoL data were not available in primary publication in 48/80 (60.0%) for-profit trials vs. 27/42 (64.3%) no-profit trials. QoL data were lacking in 48/78 (70.6%) publications of trials with overall survival as primary endpoint, 27/54 (50.0%) with other primary endpoints and 28/54 (51.9%) publications with a positive result. For trials including QoL among endpoints but lacking QoL results in primary publication, probability of secondary publication was 6.3%, 30.1% and 49.8% after 1, 2 and 3 years respectively, without evidence of improvement in time to publication comparing 2012-2015 vs. 2016-2018. Out of 83 trials including QoL, most common tools were EORTC QLQ-C30 (42, 50.6%); EORTC LC13 (39, 47.0%); EQ-5D (37, 44.6%); LCSS (19, 22.9%); FACT-L (15, 18.1%). Out of 58 trials with available results, common methods of analysis were mean scores or changes (45, 77.6%), time to deterioration (31, 53.4%) and proportion of responders (19, 32.8%). Availability of a secondary QoL publication allowed a higher number of methods of QoL analysis (p<0.001).
Conclusion
QoL is not assessed in a high proportion of phase III trials evaluating lung cancer patients, a setting where attention to QoL should be particularly high, due to symptoms and limited life expectancy. Furthermore, the timely inclusion of QoL results in primary publications is worsening in recent years. Secondary publications allow a more complete description of QoL results, but imply a delay in their availability.
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OC01 - Opening Ceremony (ID 82)
- Event: WCLC 2019
- Type: Opening Ceremony
- Track:
- Presentations: 2
- Now Available
- Moderators:
- Coordinates: 9/07/2019, 19:00 - 20:30, Barcelona (2005)
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OC01.01 - Welcome Addresses (Now Available) (ID 3551)
19:00 - 20:30 | Presenting Author(s): Giorgio Vittorio Scagliotti
- Abstract
- Presentation
Abstract not provided
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OC01.02 - IASLC Distinguished Awards (Now Available) (ID 3553)
19:00 - 20:30 | Presenting Author(s): Giorgio Vittorio Scagliotti
- Abstract
- Presentation
Abstract not provided
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P1.14 - Targeted Therapy (ID 182)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Targeted Therapy
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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P1.14-26 - ALK Fusion Variant Detection by Targeted RNA-Seq in TKIs Treated ALK-Positive Lung Adenocarcinoma (ID 1860)
09:45 - 18:00 | Author(s): Giorgio Vittorio Scagliotti
- Abstract
Background
Clinical outcomes of ALK positive (ALK+) Non-Small-Cell Lung Cancer (NSCLC) and the identification of the most effective anaplastic lymphoma kinase inhibitor (ALKi) according to the specific ALK fusion variants are not well assessed. We retrospectively characterized fusion variant distribution in a cohort of ALK+ lung adenocarcinomas (ADC) with paired clinical data about treatments and outcomes.
Method
Diagnostic tumor tissue from advanced ALK+ (by FISH and/or IHC) ADC diagnosed from 2010 to 2018 and treated with single or multiple ALKis were collected (expanded cohort from Gobbini et al. Lung Cancer, 2017). The OncomineTM Solid Tumor Fusion Transcript Kit on an Ion PGM™ system and the Ion Reporter™ software were used to identify targeted ALK fusion gene products (ThermoFisher).
Result
Specific fusion variant transcripts were found in 34/55 (62%) of collected samples. As expected, EML4-ALK fusion transcripts were the most common (31/34 samples, 91%), but HIP-ALK transcripts were also detected (3/34 - 9%). Among EML4-ALK fusions the following variants were detected: V1 (n=11); V2 (n=2); V3a/b (n=12 ) V5a/b (n=5 ) and E6A19 (n=1). Patient median age was 60 year [range 36-85], 22 were male and 12 female. Three patients were current, 11 former and 20 never smokers. Crizotinib, alectinib, ceritinib, brigatinib and lorlatinib were the ALKis used. Independently of the therapy line, 12 patients received crizotinib only, while 22 patients received crizotinib followed by one or two other ALKis. Regardless of the type of transcript, those patients who received more than one ALKi had a better median overall survival compared to those receiving crizotinib only, as expected (74 vs 21 months, HR: 5.31; 95%CI: 1.464-19.26, log rank p=0.0006). Furthermore, a significant difference in the mean duration of the different ALKi treatment was found according to the ALK variants (Chi-square p<0.0001), suggesting a private ALKi efficacy profile for specific fusion variants. Finally, the 3 HIP-ALK cases showed a better outcome with respect the EML4-ALK variants (not reached vs 51 months).
Conclusion
Our analysis suggests that different ALK fusion variant might affect ALKi treatment duration in ALK+ lung ADC.
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PR01 - Press Conference (ID 92)
- Event: WCLC 2019
- Type: Press Conference
- Track:
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/07/2019, 16:00 - 17:30, CC7.1 A&B
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PR01.07 - Lung Ambition Alliance (Now Available) (ID 3605)
16:00 - 17:30 | Presenting Author(s): Giorgio Vittorio Scagliotti
- Abstract
- Presentation
Abstract not provided
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PR03 - Press Conference (ID 94)
- Event: WCLC 2019
- Type: Press Conference
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 11:00, CC7.1 A&B
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PR03.01 - Summary of Day's Plenary (ID 4073)
10:15 - 11:00 | Presenting Author(s): Giorgio Vittorio Scagliotti
- Abstract
Abstract not provided
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YI01 - First Time Attendee Session (ID 107)
- Event: WCLC 2019
- Type: Young Investigator Session
- Track: Young Investigators
- Presentations: 1
- Now Available
- Moderators:Antonio Calles Blanco, Alan D Sihoe
- Coordinates: 9/07/2019, 07:00 - 08:30, Dublin (1997)
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YI01.02 - Why to Become a Member of the IASLC (Now Available) (ID 3691)
07:00 - 08:30 | Presenting Author(s): Giorgio Vittorio Scagliotti
- Abstract
- Presentation
Abstract
Since the 1970s, the International Association for the Study of Lung Cancer (IASLC) has promoted research and education into all aspects of lung cancer and other thoracic malignancies, as well as encouraged worldwide cancer prevention efforts.
According to its mission statement the International Association for the Study of Lung Cancer (IASLC) must embrace the study of the etiology, epidemiology, prevention, diagnosis, treatment and all other aspects of lung cancer and other thoracic malignancies; provide education and information about lung cancer and other thoracic malignancies to IASLC members, to the medical community at large, and to the public; use all available means to eliminate lung cancer and other thoracic malignancies as a health threat for the individual patient and throughout the world.
In the last ten years those goals have been embraced by a growing number of members worldwide and now the association counts on approximately 7.000 members with a large portfolio of scientific and educational activities, being now IASLC the premiere society in the field of thoracic oncology.
Beyond this bold statement the really question here is why me? While IASLC in the context of many other offers coming from other scientific organizations? The answer comes from one of our members “Being a member helped me in many, many ways. First coming to the IASLC World Conference on Lung Cancer. I was a resident and presenting in front of 100 people [….] that helped me secure my fellowship position. The IASLC helped me with great networking opportunities to interact with many members of the lung cancer community”.
That is really the key message. Inclusivity and multidisciplinary. The composition of our Board and committees reflect this sense of inclusivity. We want all the players in the thoracic oncology arena to have the appropriate voice, and the younger generation at the foremost.
IASLC mentors and support younger people in the context of several activities within the organization. IASLC has a wide range of fellowships that support people to travel and present at meetings, to get involved in research, and more importantly to get a research grant to make your ideas a reality, and to meet people who can help you further in boosting your career.
Our annual meeting is a reference meeting and every year the most relevant scientific research results have been constantly presented. The targeted therapy meeting held every year at the end of February in Santa Monica remains a unique forum of scientific exchange between researchers and pharma not paired by any other type of meeting throughout the world. Equally relevant are the regional meetings that are mainly educational but are also offering the opportunity to report about your own research.
One of the main duties of a membership association is to provide value to its members, through high quality and relevant offerings and deeper, more efficient mechanisms for engagement. Creating a robust experience for IASLC members and honoring our commitment to geographic and discipline diversity is our goal
The most challenging part for any scientific society is to understand the differences in generational needs. We need to identify the best new talents, the rising stars in our field, who will not only disrupt conventional thinking; they will lead the IASLC in the future. Specific actions will be considered and others are already in place to convince younger generations to see themselves in the IASLC mission.
We want you joining us in the fight against tobacco, we want you to be the ambassadors of our organization for the present and, more importantly, the future of our patients with the ultimate goal to be part of a dream : the eradication of thoracic malignancies
Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
