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Giorgio Vittorio Scagliotti
Moderator of
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YI 01 - Young Investigator and First Time Attendee Session (ID 588)
- Event: WCLC 2017
- Type: Young Investigator
- Track: Education/Publication/Career Development
- Presentations: 12
- Moderators:Peter Goldstraw, Giorgio Vittorio Scagliotti
- Coordinates: 10/15/2017, 08:00 - 11:30, F201 + F202 (Annex Hall)
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YI 01.01 - Introduction to IASLC: What It Can Do For You (ID 7845)
08:00 - 11:30 | Presenting Author(s): Silvia Novello
- Abstract
- Presentation
Abstract not provided
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YI 01.02 - Planning an Academic Career in Lung Cancer (ID 7846)
08:00 - 11:30 | Presenting Author(s): Navneet Singh
- Abstract
- Presentation
Abstract:
Decision making in life is not always easy. This is applicable not just for patient care but also for matters related to our own-self and is particularly true in the context of career options in medicine. Over the past few decades, the level of expertise provided by health-care providers has enhanced considerably from having comprehensive ‘all-in-one’ doctors to specialists to super-specialists and currently focused super-specialists. This has been associated with the practice of medicine having changed from ‘evidence-based-medicine’ to ‘personalized medicine’ and currently of ‘precision medicine’ and ‘tailor-made’ therapies. This has largely been based on an increase in the quantity and quality of research being conducted worldwide. A majority of this research occurs in academic medical centers/university hospitals wherein faculty/attending consultants are not just involved in patient care but have to devote a substantial percentage of their time in planning and conducting research as well as teaching undergraduate/postgraduate residents and fellows. So the natural questions that crop up for someone in training are: 1) ‘How do I decide whether I am inclined to be working in an academic institute?’ [Will I be able to ‘gel-in’ or be a complete misfit?] ‘2) What is the time-point during my training/post-training period when I need to take the decision of pursuing an academic career?’ 3) ‘What are the essential and desirable qualities/traits that are conducive to working in an academic set-up?’ There are no straightforward answers to any of these. However, generally during the final year of fellowship, most individuals are able to decide whether they would like to continue working in an academic centre or not. This is often possible with guidance from course faculty. The chief-guide under whom the individual has been pursuing research (thesis/dissertation) may be able to identify if the latter has an ‘academic bent of mind’ and provide mentorship and help the transition from ‘fellow’ (in-training) to full-time faculty [‘attending’ consultant]. It is important for anyone intending to pursue an academic career to realize that conducting and participating in research is an integral part as opposed to working in non-academic centers where patient care is the primary focus. Inclination towards research may sometimes manifest as being able to identify ‘grey’ areas in practice of medicine (clinical situations for which there are no clear-cut answers). The best researchers are and often have been those who are able to identify these areas of uncertainty related to diagnosis and treatment of a particular condition or disease and carry out research directed to answer the queries that they had in their minds when picking up these uncertainties. Keeping abreast of the latest developments in one's focus area (by regularly accessing and reading the latest publications in peer reviewed journals) as well as publishing one's own experience/research in such journals is thus part and parcel of one's job profile while working in an academic center. For lung cancer – a disease that carries the highest cancer-related mortality amongst both gender combined and the commonest cancer in males, there have been very encouraging developments in the last couple of decades and especially the last five years. We now have five pillars for treatment – targeted therapy and more lately immunotherapy coming in as very useful additions to traditional modalities (surgery, chemotherapy and radiotherapy). And these are truly exciting times for carrying out research in lung cancer in several ways: 1) Number of investigational molecules (targeted therapy and immunotherapy) being developed/tested in preclinical/clinical trials is increasing at an unparalleled rate 2) Conventional pathway followed for testing [preclinical, phase-1, phase-2, phase-3 clinical trials] is being modified to reduce time to clinical approval for successful drugs by having combined phase 1/2 or phase 2/3 trials. 3) Intense efforts are being made to expand indications for already approved/available drugs e.g. assessing utility of targeted agents in early stage/resectable NSCLC and of combination regimens (EGFR-TKIs/ALK inhibitors+ chemotherapy, PD-1/PD-L1 immune check-point inhibitors+ chemotherapy). Several unaddressed issues exist in lung cancer currently which require concerted efforts and inputs from researchers worldwide including: 1) Improving the screening algorithm for early detection such that false positive results and need for/number of invasive procedures required is reduced. Development of blood, sputum or exhaled-breath based screening tests could find greater acceptability and applicability worldwide. 2) Improving the genomic understanding of SCLC – a histological subtype without significant advances in the past leading treatment to be essentially with two modalities (chemotherapy and radiation). Identifying ‘targetable’ molecular aberrations can revolutionize management of this aggressive histological type while ongoing efforts to establish the role of immune check-point inhibitors continue. 3) Detection of EGFR sensitizing mutations and acquired T790M resistance-conferring mutation (for initiating 1[st]/2[nd] generation EGFR-TKIs and osimertinib respectively) in circulating tumor DNA (ctDNA; sometimes called circulating free tumor DNA - cfDNA) is already applicable in clinical practice and potentially can be used for monitoring treatment responses also. Next-generation-sequencing(NGS) platforms appear promising in detecting both somatic point-mutations and rearrangements/fusions with minimal tissue and/or ctDNA. Development and validation of methods for non-invasive biological monitoring of responses to chemotherapy, radiation, immunotherapy and non-EGFR targeted therapies in the complete spectrum of histological types (SCLC, squamous and non-squamous NSCLC) and disease stage distribution (neoadjuvant treatment preceding surgery, post surgery – adjuvant setting, locally advanced NSCLC following induction concurrent chemo-radiation and metastatic setting) will make it more convenient for patients and treating oncologists alike. The advantages of working in an academic setup in lung cancer are apparent both for the clinician and his/her colleagues in other clinical departments/basic sciences. Current research and clinical practice requires collaboration of different disciplines [pulmonology, diagnostic and interventional radiology (including nuclear imaging), pathology (histopathology, cytopathology, molecular pathology), thoracic surgery/surgical oncology, radiation oncology and medical oncology]. Based upon the academic institute’s geographical location, the number/work profile of departments that exist for a given discipline may vary considerably. These variations notwithstanding, the bottom-line is that reaching out to and working together with colleagues from other departments and disciplines [multidisciplinary team approach] is mandatory for attempting conduct of high-quality research and delivery of high-quality patient care in thoracic oncology. This potential advantage and benefit also comes with several challenges. One is required to carefully balance and utilize working hours for patient care, research and training while attempting to do the best in all three fields. This invariably, if not mandatorily, leads to spill-over of work into ‘off-work’ hours and impinges on ‘family-hours’ or ‘personal-time.’ The support of one's spouse, parents and children in such settings cannot be undermined or understated. One needs to keep a balance between ‘All-work-and-no-play makes Jack a frustrated man’ versus ‘Jack-of-all-trades and master-of-none’. Neither is desirable and the ultimate aim is to have a satisfying career in thoracic oncology while working in an academic setting wherein one is able to: 1) provide patients (often under-privileged and belonging to poor socio-economic strata) the best diagnostic and treatment facilities (despite presence of resource constraints) – Patient Care 2) be involved in clinically relevant basic and translational research that has the potential to improve patient care in one’s own geographical location – Research 3) share one’s experience with residents/fellows and colleagues within the institute and outside – Medical Education Navneet Singh MD DM Email: [The author is a thoracic medical oncologist-cum-pulmonologist currently working as an Associate Professor of Pulmonary Medicine at the Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India. He is a member of IASLC’s Staging & Prognostic Factors Committee; Publications Committee and is IASLC’s Regent for the Indian Subcontinent. Additionally, he is Chair-Elect of the American Society of Clinical Oncology’s (ASCO) International Development and Education Award (IDEA) Working Group and a member of its Multidisciplinary Cancer Management Course Working Group and Thoracic Cancer Guideline Advisory Group. His detailed profile is accessible at http://www.linkedin.com/in/navneet-singh-160012.]
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YI 01.03 - Community versus Academic Oncology (ID 7847)
08:00 - 11:30 | Presenting Author(s): Philip Bonomi
- Abstract
- Presentation
Abstract:
Relatively little information is available for hematology oncology fellows to inform their choice for an academic oncology(AO) vs a community oncology(CO) career. In 2006, Desch and Blayney(1) described practical differences between AO and CO careers which are still pertinent today. A more recent report from Vanderbilt(2) describes factors which appear to influence oncology fellows’ career decisions. Once a career path has been selected, does this choice affect career and work-life balance satisfaction? Shanafelt and his colleagues have described the impact of career choice and related factors on job satisfaction(3,4). This review will summarize the results of these reports and share a perspective regarding possible changes in oncology practices which could impact career choice. Desch and Blayney(1) describe mission, governance, patient care, financial considerations, referral bases, career flexibility, and determinants of success. The mission for community oncologists(COs) consists of delivering excellent patient care and running a successful business. In contrast, the mission for academic oncologists(AOs) encompasses patient care, research and teaching. CO governance offers more autonomy and usually consists of a doctor owned corporation with equal ownership. AOs work in a hierarchical system with multiple levels between the physician and senior leadership. There are significant differences in delivering patient care. Desch and Blayney point out that “ COs are intern, resident, fellow, and attending all rolled into one. ” COs have more weekend and night call. In addition, COs provide care for multiple types of cancer patients , while AOs’ practice is usually limited to one or two types of malignancy. Patient referrals for COs depend upon building relationships with primary care physicians and surgeons in their community. AOs also get patient referrals from primary care physicians and surgeons, but they rely heavily on institutional reputation, the reputation of disease specific experts, and a robust clinical trial program. Publishing and giving presentations at local and national meetings establishes AOs as disease specific experts which results in physician referrals and in patient initiated consultations. Revenue for COs depends upon fees for physician services, for administration of intravenous treatment , for laboratory tests, for imaging, and revenue from chemotherapy/immunotherapy treatments. For AOs, revenue comes from fees for physician services, grants, clinical trial revenue, and philanthropy. In some academic institutions, revenue may also come from the ancillary sources, similar to private practice. Starting and subsequent compensation is higher for COs who receive significant salary increases when they become full partners in the corporation, 2-5 years after joining the practice. Salary for AOs increases with increasing academic rank and may be supplemented with bonuses and honorariums for lectures and participation in advisory boards. Desch and Blayney(1) suggest that there are critical success factors for COs and AOs. . Building a reputation as a local expert and being readily available to referring MD’s and partners is essential for COs. . They also point out that it is essential for COs to invest time to understand bonuses and to show that they value and support the practice staff. AOs must focus on area of expertise, choose a good mentor, publish results of research, and apply for grants. It is not realistic to expect AOs with a large clinical practice to be the principal investigator on a grant. However, these clinicians can learn the concepts of basic science and partner with laboratory investigators in translational research grant proposals. Horn and her collegues(2) studiedfactors associated with selecting an AO or CO career. They invited program directors at 56 NCI designated and National Comprehensive Cancer Network cancer centers. Fellows at these institutions were asked to complete a questionnaire regarding their interest in AO vs CO careers. . Fellows with a high interest in AO were more likely to be women, have an additional graduate degree, and to have participated in basic research. Also fellows who were more interested in AO gave more presentations at scientific meetings and had more publications. Having an influential mentor and a desire to teach were also related to pursuing a career in AO. . Fellows who were more interested in CO were motivated by work-life balance and autonomy. This study suggest that fellows who are primarily motivated by being involved in identifying new information and teaching are more likely to pursue AO , while fellows who are motivated by favorable work-life balance and having more autonomy are more likely to pursue a CO career. How do practicing oncologists feel about their careers? Shanafelt and colleagues(3,4) have published two reports describing results of a survey which evaluated burnout, career satisfaction, life – work balance satisfaction and retirement. They(3) found that COs spent more time in clinic and saw more patients.. Younger age and more hours in clinic were associated with increased risk of burnout, which was defined as a combination of emotional exhaustion and depersonalization (loss of concern for patients),. There was a trend for higher rate of emotional exhaustion and a significantly higher rate of depersonalization in community oncologists. Although the majority of oncologists would choose a career in oncology, there was a higher number of COs who stated they would not choose an oncology career. In the second report(4), they did not compare AOs and COs. They saw that although most oncologists find meaning in their work, 52% were dissatisfied with work-life balance. “They like their work but want to do less of it.” Work-life balance was affected by more night and weekend call, while method of compensation salary +/- bonuses (most AOs) versus incentive (most COs) was not related work-life balance. For oncologists who planned to reduce work hours, the most common reason was to spend more time with family. In summary, when making a career choice, oncology fellows should identify what motivates them. I suspect that the majority of oncologists will continue to be happy with their career choice and that the current differences between AO and CO careers may decrease because more COs will be employed by hospital systems. References 1.Desch CE, Blayney DW. Making the Choice Between Academic Oncology and Community Practice: The Big Picture and Details About Each Career. Oncol Pract 2:132-138, 2006 2.Horn L, Koehler E, Gilbert J, et al. Factors Associated with the Career Choices of Hematology and Medical Oncology Fellow Trained ar Academic Insitutions in the United States. J Clin Oncol 29: 3932 - 3938, 2011 3.Shanafelt TD, Gradishar WJ, Kosty M, et al.Burnout and Career Satisfaction Among US Oncologists. J Clin Oncol 32: 678-686, 2016 4.Shanafelt TD, Raymond M, Kosty M, et al.Satisfaction with Work-Life Balance and the Career and Retirement Plans of US Oncologists.J Clin Oncol 32:1127-1135, 2014
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YI 01.04 - Clinical Trials 101 (ID 7848)
08:00 - 11:30 | Presenting Author(s): Julie R Brahmer
- Abstract
- Presentation
Abstract not provided
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YI 01.05 - Investigator Initiated Trials (ID 7849)
08:00 - 11:30 | Presenting Author(s): Daniel SW Tan
- Abstract
- Presentation
Abstract not provided
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YI 01.07 - How to Get Your Paper Published (ID 7850)
08:00 - 11:30 | Presenting Author(s): Alex Adjei
- Abstract
- Presentation
Abstract not provided
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YI 01.08 - Why Should I Publish? An Overview of the Manuscript Cycle: From Submission to Publication (ID 7851)
08:00 - 11:30 | Presenting Author(s): Jim Jett
- Abstract
- Presentation
Abstract not provided
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YI 01.09 - How to Prepare an Abstract for an International Conference and How to Prepare Your Presentation for the Conference (Tips and Tricks) (ID 7852)
08:00 - 11:30 | Presenting Author(s): Michael Boyer
- Abstract
- Presentation
Abstract not provided
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YI 01.10 - How to Write a Grant Application for Young Investigators (ID 7853)
08:00 - 11:30 | Presenting Author(s): Heather A Wakelee
- Abstract
- Presentation
Abstract:
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YI 01.11 - The Young Investigator Travel Award Experience - A Report from a Previous Award Winner (ID 7854)
08:00 - 11:30 | Presenting Author(s): Takahiro Karasaki
- Abstract
- Presentation
Abstract:
I received the WCLC 2016 Young Investigator Travel Award for my presentation entitled “Immunogram for cancer-immunity cycle towards personalized immunotherapy of lung cancer”. It was my great honor to receive the award, and I want to thank the conference committee and all the conference attendees. This was my first time to attend the WCLC, and I enjoyed the conference and my stay in Vienna. I was given the opportunity to join the Faculty Dinner held in Vienna City Hall. It was a fabulous experience, and I thoroughly enjoyed sitting at the same table as world-renowned surgeons and oncologists. During the conference, I mainly attended immunotherapy sessions where I learned about the results of the most recent clinical studies. Furthermore, while attending the biomarker session, I realized that biomarkers in this field are still inadequate and the development of useful biomarkers in immunotherapy is an urgent need. Receiving the young investigator scholarship has encouraged me to continue our efforts to unveil the tumor microenvironment in each patient using individual next-generation sequencing data in order to develop “next-generation biomarkers” and achieve optimal personalized immunotherapy. Last year, in a Perspectives article in Science, Blank et al. proposed the concept of the cancer immunogram, a framework to illustrate multiple parameters that influence the cancer-immunity interaction (1). In their article, the concept was applied theoretically to patients but not tested in practice. To accomplish this, we developed an immunogram reflecting the cancer immunity cycle using next-generation sequencing data, and applied it to real patients with lung cancer. An immunogram for the cancer immunity cycle is a radar chart that consists of eight molecular profiles relevant to the development of T-cell immunity to tumor cells. We sought to translate cumbersome omics data into easily comprehensible “report cards” for clinicians. Immunograms can be used as integrated biomarkers, and may become a valuable resource for optimal personalized immunotherapy. After the presentation at the WCLC 2016, our findings were published in the Journal of Thoracic Oncology in May (2). It was an honor that our article was chosen by the Editor to be a featured article and was introduced by an elegant review (3). We recently updated our method by normalizing the immunogram score using TCGA data. We are pleased to share the details of this improvement during the present conference. Although we are working in a challenging field and there is still a long way to go, we are encouraged by the award and will continue to struggle toward further breakthroughs. References (1) Blank CU, Haanen JB, Ribas A, Schumacher TN. Cancer immunology. The “cancer immunogram” Science. 2016;352:658-60. (2) Karasaki T, Nagayama K, Kuwano H, et al. An Immunogram for the Cancer-Immunity Cycle: Towards Personalized Immunotherapy of Lung Cancer. J Thorac Oncol.2017;12(5):791-803. (3) Botling J, Sandelin M. Immune Biomarkers on the Radar-Comprehensive "Immunograms" for Multimodal Treatment Prediction. J Thorac Oncol.2017;12(5):770-2.
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YI 01.12 - Making the Most of the WCLC: A Guide for First Time Attendee - From an Expert Perspective (ID 7855)
08:00 - 11:30 | Presenting Author(s): Suresh Senan
- Abstract
- Presentation
Abstract not provided
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YI 01.13 - Making the Most of the WCLC: A Guide for First Time Attendee - From a Second Time Attendee (ID 7856)
08:00 - 11:30 | Presenting Author(s): Deepali Jain
- Abstract
- Presentation
Abstract:
The IASLC (International association for the study of lung cancer) WCLC (World Conference on Lung Cancer) is world’s largest academic platform dedicated for the study of lung cancer and other thoracic malignancies which not only caters to physicians but also includes active participation from each discipline of medicine involves in patient care. In addition health advocacy groups and patients will also join WCLC to obtain and exchange the information. The focus of the meeting is on the biology, diagnosis, pathogenesis, treatment and management of lung cancer so to begin from active prevention and accurate diagnosis to advanced care. Because of advancing science of lung cancer, IASLC decided to hold WCLC every year so people will be kept abreast with the current knowledge and updates in this field. There are many academic opportunities for the young investigators or first-time attendee to pursue their career in the field of thoracic oncology. They can meet the experts during the conference, attend various educational sessions and take guidance in the field of basic, translational and clinical research. There are many awards which help in not only enhancement of academic career but also in attending conference from resource poor countries. Travel awards given to developing nation investigators so that they can attend the conference and present their latest research in addition to make collaborations and academic networking. International mentorship program of IASLC is very useful professional development and education program for early-career doctors from economically-developing countries in which you get an opportunity to spend a week time in a well established hospital or laboratory under the mentorship of an international expert in that field. This year, the Core Program Committee has organized a scientific program that includes more than 450 presentations. The conference motto is “Synergy to Conquer Lung Cancer” which will be very overwhelming at both scientific and educational fronts. The education sessions include state-of-the-art talks by experts on academically challenging and evolving topics. The scientific program includes research presentations in the form of posters and platform formats. There are many events and platforms where first time attendees can interact and do networking for future collaborations. It is certain that the 18[th] WCLC will help young investigators and first time attendees to build and shape-up their career in thoracic oncology.
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MA 19 - Mesothelioma: Bench to Bedside (ID 680)
- Event: WCLC 2017
- Type: Mini Oral
- Track: Mesothelioma
- Presentations: 1
- Moderators:Dean A Fennell, Hedy Lee Kindler
- Coordinates: 10/18/2017, 11:00 - 12:30, Room 315
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MA 19.03 - Nintedanib + Pemetrexed/Cisplatin in Malignant Pleural Mesothelioma (MPM): Phase II Biomarker Data from the LUME‑Meso Study (ID 8111)
11:00 - 12:30 | Author(s): Giorgio Vittorio Scagliotti
- Abstract
- Presentation
Background:
Nintedanib is a triple angiokinase inhibitor. LUME-Meso (NCT01907100) is a randomised, Phase II/III study of ≤6 cycles of nintedanib+pemetrexed/cisplatin versus placebo+pemetrexed/cisplatin, followed by nintedanib or placebo maintenance, in chemo-naïve patients with MPM. In Phase II results, nintedanib+pemetrexed/cisplatin improved progression-free survival (PFS) versus control (hazard ratio [HR]=0.54; p=0.010), with a trend for prolonged overall survival (OS; HR=0.77; p=0.319). Benefit was most pronounced in patients with epithelioid tumours. Since no pharmacodynamic/predictive biomarkers are validated for anti-angiogenic therapies, exploratory analyses were conducted to investigate potential associations of plasma-derived angiogenic factors and genomic markers with treatment outcome in the LUME-Meso Phase II epithelioid population.
Method:
Blood samples were collected at baseline and, for patients receiving maintenance, at monotherapy Cycle 3 (C3mono) and end of monotherapy (EoTmono). Analyses focused on 58 angiogenic factors (Human AngiogenesisMAP[®] panel, Myriad RBM) and single-nucleotide polymorphisms (SNPs) in genes implicated in mesothelioma and/or associated with response to anti-angiogenic therapies in other tumour types (VEGFR1, VEGFR3 and mesothelin). Associations of biomarkers with treatment effect were evaluated by Cox regression and tested for interaction with false discovery rate (FDR) adjustment. Adjusted mean changes in angiogenic factor levels were compared between arms by ANCOVA. Analyses were exploratory, limited by small sample size, and considered hypothesis generating.
Result:
Of 77 patients with epithelioid tumours, angiogenic factor and genomic data were available for 71 and 67 patients, respectively. PFS/OS benefit of nintedanib appeared potentially more pronounced in patients with baseline plasma endoglin level below the median. There were possible weak associations between major homozygous genotypes for two VEGFR3 SNPs (rs307821 G/G and rs307826 A/A), and OS benefit and between VEGFR1 SNP rs9582036 A/A genotype and PFS benefit. Biomarker treatment associations were limited by small subgroup size, especially for low-frequency SNPs, and interaction tests were not significant after FDR adjustment. Regarding pharmacodynamic effects, adjusted mean change in interleukin-8 levels with nintedanib was greater from baseline to C3mono and lower from C3mono until EoTmono, compared with placebo. Nintedanib showed lower adjusted mean changes versus placebo for VEGFR2 from baseline to C3mono, and for VEGFR2 and VEGFR3 from baseline to EoTmono.
Conclusion:
These analyses represent the first biomarker results for nintedanib-treated MPM. While there seemed to be signals for greater PFS and OS improvement in patients with low plasma endoglin and major homozygous VEGFR1/3 genotypes, no biomarkers showed clear significant association with treatment benefit. These findings warrant further evaluation in the Phase III study.
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P1.09 - Mesothelioma (ID 695)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Mesothelioma
- Presentations: 1
- Moderators:
- Coordinates: 10/16/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P1.09-011 - LUME-Meso Phase II/III Study: Nintedanib + Pemetrexed/Cisplatin in Chemo-Naïve Patients with Malignant Pleural Mesothelioma (ID 7937)
09:30 - 16:00 | Author(s): Giorgio Vittorio Scagliotti
- Abstract
Background:
Pemetrexed/cisplatin is the standard first-line treatment for unresectable malignant pleural mesothelioma (MPM), with median overall survival (OS) of ~1 year. Nintedanib is a triple angiokinase inhibitor of vascular endothelial growth factor (VEGF) receptors 1–3, platelet-derived growth factor (PDGF) receptors α/β and fibroblast growth factor receptors 1–3. VEGF and PDGF overexpression are associated with poor prognosis in MPM, and nintedanib has demonstrated efficacy in preclinical MPM models. Nintedanib also targets the Src and Abl kinases, which are involved in MPM cell migration. A randomised Phase II trial of nintedanib or placebo + pemetrexed/cisplatin in MPM followed by maintenance nintedanib or placebo, with progression-free survival (PFS) as the primary endpoint, was performed. With regulatory authority guidance, the Phase II data were unblinded. At the primary analysis, PFS benefit was observed with nintedanib, and confirmed at the updated analysis (hazard ratio [HR]=0.54, 95% confidence interval [CI]: 0.33–0.87; p=0.010; median PFS: nintedanib 9.4 months vs placebo 5.7 months). A strong signal towards improved OS also favoured nintedanib (HR=0.77, 95% CI: 0.46–1.29; p=0.319; median OS: 18.3 vs 14.2 months). The study was expanded to include a confirmatory Phase III part based on the primary PFS results, and the Phase II data assisted in planning of the Phase III part, including sample size estimation. Nintedanib was granted US Food and Drug Administration orphan drug designation for the treatment of MPM in December 2016.
Method:
The Phase III part of the study (NCT01907100) is currently recruiting participants. Four hundred and fifty chemotherapy-naïve patients worldwide (~140 sites in 27 countries), aged ≥18 years with unresectable MPM of epithelioid histology and Eastern Cooperative Oncology Group performance score 0–1 will be randomised 1:1 to receive up to six 21-day cycles of pemetrexed (500 mg/m[2])/cisplatin (75 mg/m[2]) on Day 1 + nintedanib or placebo (200 mg twice daily, Days 2–21), followed by nintedanib or placebo monotherapy until disease progression or undue toxicity. The primary endpoint is PFS with the key secondary endpoint being OS. An adaptive design will be used at the time of the primary PFS analysis to reassess the number of OS events for sufficient OS power. Other secondary endpoints are objective response and disease control (using modified Response Evaluation Criteria in Solid Tumors). The frequency and severity of adverse events, as well as health-related quality of life, will also be assessed. An exploratory analysis of predictive/prognostic biomarkers is planned.
Result:
Section not applicable
Conclusion:
Section not applicable
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P2.09 - Mesothelioma (ID 710)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Mesothelioma
- Presentations: 1
- Moderators:
- Coordinates: 10/17/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P2.09-003 - Dissecting the Immune Environment in Malignant Pleural Mesothelioma: Results from a Prospective Assessment (ID 8256)
09:30 - 16:00 | Author(s): Giorgio Vittorio Scagliotti
- Abstract
Background:
Malignant pleural mesothelioma (MPM) cells grow in the context of immune cells, either infiltrating the tumor or present in the associated pleural effusion. Specific immune cell subsets and immune-checkpoints on T-lymphocytes infiltrating the tumor have been proposed as possible prognostic factors (Uiije, DOI:10.1080/2162402X.2015.1009285; Awad, DOI:10.1158/2326-6066.CIR-16-0171) and therapeutic targets (Marcq, DOI:10.1080/2162402X.2016.1261241; Khanna, DOI: 10.1016/j.jtho.2016.07.033). The immune cells infiltrating MPM are however dynamically exchanged with those present in the pleural fluid (Lievense, DOI: 10.1016/j.lungcan.2016.04.015). The heterogeneity of tumor bulk, ranging from terminally differentiated cells to tumor-initiating cells (TIC), makes the interactions between tumor and immune cells even more jeopardized. Our study is the first that analyzes at the same time the immune-phenotype of MPM cells, immune cells infiltrating the tumor and present in the matched pleural fluid, to obtain a comprehensive signature of MPM immune-environment and precise indications for personalized immunotherapy-based interventions.
Method:
From June 2015 to June 2017, we collected 120 pleural fluids and biopsies from patients that undergone diagnostic thoracoscopy: 34 samples were diagnosed as MPM (25 epithelioid, 5 sarcomatoid, 4 biphasic MPM), 56 samples were reactive non neoplastic pleuritis, 30 samples were pleural localization of lung adenocarcinoma or other tumors. Cells of pleural fluids were analyzed by cell sorting and flow cytometry. Biopsies were cut and digested, and cell populations were analyzed as well. We isolated, expanded and analyzed the TIC-component from 5 epithelioid and 5 sarcomatoid MPM.
Result:
MPM significantly differed from non neoplastic pleuritis for the increased number of CD3[+]CD8[+]T-lymphocytes in pleural essudate coupled with the reduction of this population within the tumor (p<0.001). M2/M1-macrophages ratio was also higher (p<0.02). The increased number of T-regulatory cells and granulocytic/monocytic myeloid-derived suppressor cells in both pleural fluid and tumor significantly (p<0.005) differentiated MPM from non neoplastic pleuritis and other malignancies. Either CD3[+]CD8[+]or CD3[+]CD4[+]T-lymphocytes present in pleural fluid and infiltrating the tumor had higher expression of PD-1, LAG-3, TIM-3 immune-checkpoints (p< 0.02), coupled with increased expression of PD-1L, LAG-3, TIM-3 and GAL-9 on matched MPM (p<0.05) compared to non neoplastic pleuritis. Interestingly, immune-checkpoints were down-regulated in TIC, suggesting that immune-checkpoint inhibitors may be poorly effective against this MPM component.
Conclusion:
Our study identified an immune-signature that discriminates MPM from pleuritis secondary to other tumors or non malignant diseases. Such immune-signature will help to refine prognostic factors and define a precision immunotherapy for MPM.
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PL 04 - Closing Plenary: Where We Are Now, and Where We Will Be in 10 Years (ID 587)
- Event: WCLC 2017
- Type: Plenary Session
- Track:
- Presentations: 1
- Moderators:H. Kato, Rafael Rosell
- Coordinates: 10/18/2017, 16:30 - 17:45, Main Hall
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PL 04.03 - Where We Are Now, and Where We Will Be in 10 years: From European Perspective (ID 7843)
16:30 - 17:45 | Presenting Author(s): Giorgio Vittorio Scagliotti
- Abstract
- Presentation
Abstract not provided
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