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Teresa Moran
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ES18 - Acquired Resistance to TKIs: The Rebiopsy Case and the Future Options (ID 21)
- Event: WCLC 2019
- Type: Educational Session
- Track: Targeted Therapy
- Presentations: 4
- Now Available
- Moderators:Teresa Moran, Matteo Giaj Levra
- Coordinates: 9/09/2019, 11:00 - 12:30, Vienna (2016)
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ES18.01 - Rebiopsy in Oncogene Addicted NSCLC at Progression (Now Available) (ID 3252)
11:00 - 12:30 | Presenting Author(s): D. Ross Camidge
- Abstract
- Presentation
Abstract
As we have defined piecharts of different oncogenes at diagnosis in NSCLC, each oncogene, under the selection pressure of an active targeted agent may develop acquired resistance after initial benefit in a number of different ways, allowing intra-oncogene piecharts of acquired resistance mechanisms to be described.
Key features to consider when considering a rebiopsy - either of the tumor or of a surrogate of the tumor (cf-DNA) is the ease and risks of rebiopsy, its false positive and false negative rates and the potential 'actionability' of the data generated. These factors allow rebiopsies for research purposes to be differentiated from those that could inform changes in clinical care immediately.
Rebiopsies of systemic disease, became standard when osimertinib was used post 1st- or 2nd-generation EGFR TKIs to look for T790M. With the move of osimertinib to the first line setting, the need to detect T790M has becoem less, but other mechanisms of resistance in the post 1/2nd generation EGFR TKI setting, separate from T790M, and in the post-osimertinib setting including small cell transition and MET amplification are also likely to change clinical management and maintain the role for biopsies in EGFR mutant disease.
In ROS1 rearranged lung cancer - the lack of efficacy of lorlatinib and crizotinib to G2032R clinically, but the possible activity of repotrectinib in trials, can make the case for a rebiopsy and reanalysis post-crizotinib or lorlatinib in ROS1+ disease. Actionable second drivers remain under exploration.
In ALK rearranged lung cancer, on target mutations are multiple - preclinical data suggesting specific drugs for specific mutations post-crizotinib can be identified remains partially determined, with multiple caveats about the preclinical-clinical transferability of data. The ALK master protocol will address some of these issues. However, perhaps the biggest issue relates to the potential for non-ALK related second drivers to be actionable, suggesting the methodology of testing in the acquired resistance setting, as in EGFR, should be broad.
Rebiopsies performed in the setting of CNS progression, in the absence of prior overt CNS benefit, are of limited practicality or use at present, however, with the advent of CNS penetrant drugs for key oncogenes, true CNS acquired resistance may emerge and some form of CNS sampling may become relevant.
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ES18.02 - When to Switch to a New TKI : Imaging Based Crtieria or Positive Liquid Biopsy? (Now Available) (ID 3253)
11:00 - 12:30 | Presenting Author(s): James Chih-Hsin Yang
- Abstract
- Presentation
Abstract
The discovery of specific mutations and associated addicted pathways in lung adenocarcinoma cells has led to the development of many targeted therapies useful for corresponding activating mutation. In addition, conventional chemotherapy and novel immunotherapy such as PD1/PDL1 antibodies are also very effective for lung cancer patients with or without specific driver mutation. Patients with metastatic lung cancer nowadays can be treated with multiple lines of effective treatment. Patients who receive more lines of therapy tend to live longer than those who had only receive limited number of treatment. In order to maximize the overall survival outcome of metastatic lung cancer patient who receives systemic treatment, it is important to find out the best first line choices and the best timing to change the treatment regimen to second line and so forth. Tumor reduction or stabilization by imaging criteria has been used widely for a long time in chemotherapy and targeted therapy era. RECIST (Response evaluation criteria in solid tumors) has been adopted as a uniform criteria for cancer clinical trial to classify the tumor response to certain treatment. However, in order to accommodate different cancer types and sites of metastasis, several variants of RECIST emerged to better evaluate the treatment response and necessity of maintain the present treatment. In daily practice, changes of tumor size in the image provide the best guidance for clinicians to continue or change regimen for the patients. In patients who has no reliable evaluable radiological image for follow up, such as patients who presented with effusion, bone metastasis, leptomeningeal metastasis or tumor with poor margin, patients’ clinical performance and alterations in tumor markers occasionally can provide clinicians information for judgement. The introduction of cell free plasma tumor DNA for the molecular diagnosis of cancer gave us a new change of how to manage the patients properly when changing regimen to prolong patients chance to survive or improving quality of life are attainable. There are a least 3 important applications for cell free tumor DNA detection. First is to provide information of specific mutation at the time of diagnosis or progression, so that a corresponding targeted therapy can be chosen as the best treatment of choice. Second is to use quantitative amount of specific mutation found in plasma cell free DNA to follow patient’s tumor. The presumption is the amount of specific mutation may represent the tumor load of the treated patients. The 3rd possible application is to use the novel mutations detected in the plasma at the time of diagnosis or during treatment follow up to select a theoretical best combination for patients. There are ample of analysis reported in the literature for the first and second possible applications of plasma cell free DNA. The evidence for the 3rd possible application is accumulating. However, there is no emphasis of using this vast information gathered in the plasma to guide the right timing to switch regimen. In addition, there has been a trend to continue original treatment in slow progressing patients beyond imaging progression, or to treat oligo-progressing sites with local irradiation or surgery in order to keep the original treatment. These approaches certainly will further complicate the rationale decision of right timing to change regimen. Thus, a few options exist for patients who are receiving targeted therapies. One is to use conventional ways of RECIST progression by imaging studies to change the treatment to further lines. The treatment outcome may be more predictable, because most of the clinical trials follow this dogma. A second choice is to treat patients beyond progression by RECIST and follow physicians judgment to switch the regimen. Several recent clinical trials use this criteria to change regimen and collect the treatment time as duration-of-treatment, or time-to-treatment-failure. The 3rd possible timing is to switch regimen according to plasma DNA alterations, for example, emergence of activating mutation when plasma tumor DNA was previously eradicated by current targeted therapy; add another targeted therapy when a new parallel pathways amplification is predicted from the plasma sample analysis. This strategy lack the support of prospective clinical trial data and was purely based on direct scientific deduction or instinct and a few case reports. Therefore, studies specifically designed to address the switch timing is very important. Unfortunately, the effort devoted to this area is lacking.
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ES18.03 - New Strategies to Overcome Resistance in EGFR Mutated NSCLC (Now Available) (ID 3254)
11:00 - 12:30 | Presenting Author(s): Paul A Bunn, Jr
- Abstract
- Presentation
Abstract
New Strategies to Overcome Resistance in EGFR Mutated NSCLC
Activating EGFR mutations occur in 15-50% of lung adenocarcinomas with a higher frequency in never or light smokers and individuals of East Asian origin. First and second generation EGFR tyrosine kinase inhibitors (TKI) such as gefitinib, erlotinib, afatinib and dacomitinib are associated with high response rates (50-75% and median progression free survival rates of 9-14 months. Failure in the CNS is frequent because these agents have poor CNS penetration and the most frequent cause of systemic failure is the development of T790M resistance mutations. Other reported mechanisms of resistance to first and second generation EGFR TKIs include small cell transformation, AXL overexpression, HER2 mutation and overexpression, Wnt pathway overexpression and other less common alterations. Standard platinum doublet chemotherapy is generally used for those with small cell transformation and these cases usually have Rb loss and p53 mutation. The addition of cetuximab to first or second generation EGFR TKIs did not appear to improve outcomes.
Osimertinib is a third generation EGFR TKI whose advantages include high sensitivity to both activating EGFR mutations and T790M mutations with lesser sensitivity to wild type EGFR. Osimertinib also crosses the blood brain barrier. A randomized phase III trial, AURA3, demonstrated that osimertinib was superior to chemotherapy and was associated with decreased CNS relapse in the second line setting after failure on a first generation EGFR TKI due to T790M.
These data with second line osimertinib led to a first line phase III randomized trial, FLAURA, comparing osimertinib to either gefitinib or erlotinib. Osimertinib was associated with a significantly longer PFS, a significantly longer time to CNS progression, a significantly longer duration of response and a longer overall survival that had not reached significance at most recent analysis. Patterns of resistance to first line osimertinib are only emerging now but include alterations that have specific targeted therapy such as MET amplification (15%), BRAF mutations (3%), HER2 amplification (1%), ALK fusions (1%), PI3K mutations (3%), KRAS mutations (2%), C797s or other resistance mutations (2%), SCLC transformation (5%), CDK and cell cycle alterations (2-5%). Because these have specific non-chemotherapy treatment options, NGS testing should be done on blood ctDNA and if negative on tissue at the time of progression.
For those without these actionable alterations, chemotherapy is the next standard therapy although combinations of chemotherapy with checkpoint inhibitors with or without anti-VEGF agents is under investigation due to a positive subset analysis of the IMPOWER 150 trial. The addition of checkpoint inhibitors to first line TKIs has proven to have increased toxicity with low activity.
Another way to delay or prevent resistance is to use combinations in the first line therapy. Combinations of EGFR TKIs with anti-VEGF therapies, with anti-MET therapies, with anti-EGFR antibodies, and with chemotherapy are in progress. Initial trials combining erlotinib with bevacizumab demonstrated improved PFS but not OS. Current trials are combining newer EGFR TKIs such as osimertinib with anti-VEGF antibodies such as bevacizumab or ramicirumab are in progress. Trials using anti-VEGFR TKIs are also in progress. Preclinical studies indicated that combining anti-EGFR antibodies such as cetuximab or necitumumab with EGFR TKIs could overcome some resistance led to other ongoing clinical trials combining these agents. Amplification of MET is a common mechanism of resistance to EGFR TKIs, so the combination of MET TKIs with EGFR TKIs is rational and trials are ongoing. Understanding the mechanisms by which EGFR mutant cells can persist in the presence of initial EGFR TKIs remains a priority for future investigation.
The adjuvant use of EGFR TKIs after surgical resection of early stage NSCLC patients with EGFR mutations has clearly established superiority in recurrence free survival but not in overall survival. It appears that there is insufficient cell kill to lead to an increase in the cure rate but additional survival based adjuvant trials such as ”ALCHEMIST” are ongoing.
Neoadjuvant studies could provide downstaging because the response rates are high. It is not clear whether this would be more likely to provide an increase in cure rates compared to adjuvant use of these agents. These neoadjuvant trials are providing surgical samples to explore mechanisms by which cells persist after EGFR TKI therapy. This incredibly important information could lead to rational combinations that could increase pCR rates in early stage patients and improved outcomes in advanced stage patients.
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ES18.04 - New Strategies to Overcome Resistance in ALK Rearranged NSCLC (Now Available) (ID 3255)
11:00 - 12:30 | Presenting Author(s): Sai-Hong Ignatius Ou
- Abstract
- Presentation
Abstract
Since the discovery of ALK+ NSCLC in 2007, there are now 6 ALK TKI have been approved or in clinical development. These 6 ALK TKI can be generally divided into 3 generations. First-generaion (Crizotinib). Second Generaion (Alectinib, Ceritinib, Brigatinib, Ensartinib). THrid-generation (Lorlatinib). The advantages of the second-generation ALK TKI or beyond is better potentcy an excellent improved CNS penetration. The mode of progression in ALK+ NSCLC are 4 fold and can be single or combination according to individaul patients: developed of acquired second site ALK mutations, CNS progression, bypass activation, and histological transformation.
For second site ALK mutations, sequencing ALK TKIs that will overcome the particular second site mutation(s) or proceed to the most potent ALK TKI is likley be successful.
For CNS progression, lorlatinib has demonstrated CNS activity in CNS progression from second generation ALK TKIs (ceritinib, alectinib). Additionally the use of stereotactic radiation (SRS) or whole brian radiation can contral CNS progression but clinicians should look out for radiation necrosis.
For second bypass activation such as (i.e. RAS, SRC, EGFR, Kit) in vritro pre-clinical modles of combining specific bypass inhibitor and ALK TKI were albe to inhibit growth of these resistance cell lines or patient dervied PDX model, clinical trials are on-going but to date clinical data are lacking. Additional the use of chemotherapy especailyl pemetrexed-based chemotherapy in addition to ALK TKI has showen to be more efficacious than just switching to chemotherapy while discontinuing ALK TKI
For histologic transformation most commonly small cell transformation, the switching to small cell regimen is only viable option at this point. The addition to immunotherapy to chemotherapy (e.g. IMpower133 regimen) or IO + IO combination (e.g. chckmate-032) should be explored in small cell tranformation as mode of progression in ALK+ NSCLC.
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Author of
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EP1.01 - Advanced NSCLC (ID 150)
- Event: WCLC 2019
- Type: E-Poster Viewing in the Exhibit Hall
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
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EP1.01-37 - Platinum-Based Chemotherapy (CT) Rechallenge in Advanced Non Small Cell Lung Cancer (NSCLC) Patients (p): A Single Institution Experience (ID 2689)
08:00 - 18:00 | Author(s): Teresa Moran
- Abstract
Background
No phase III trials have been carried out to prove the value of a platinum-doublet rechallenge in p with NSCLC. Currently, the availability of different effective drugs makes the platinum-based salvage therapy unusual. Moreover, the potential cumulative toxicity related to cisplatin or carboplatin can be an issue. However, retreatment with platinum-based CT could be hypothetically proposed for p with a long time to progression (TTP) from the last platinum treatment, in p with a good performance status, who may be symptomatic and with no formal contraindication to receive such treatment We have retrospectively reviewed experience at our institution of platinum-based chemotherapy rechallenge in stage III and IV NSCLC p
Method
A cohort of 376 p with stage III and IV NSCLC treated with first-line platinum doublets from January 2012 to December 2017 were included. We extracted information on clinical and molecular characteristics, as well as treatment details. Time to progression was evaluated by Kaplan-Meier curves and groups were compared using Log-rank test.
Result
Overall, 57 p were rechallenged with platinum-based CT (group A). Median age was 57 years (51.5-65) for rechallenged p versus (vs) 62 (56.2-68.8) for the entire cohort (group B)[p=0.001]. Group A include more p with stage III p( 54.4% vs. 30.7%; p=0.001), as well as more p with better ECOG Performance Status (PS) (PS 0 70.2% vs. 44.5%; p=0.001). No differences in gender, smoking status, histology and comorbidities were observed between both groups (20.7% and 29.8% were women and 38.6% and 53.9% were smokers in groups A and B, respectively).
No differences in molecular profile (EGFR, ALK, ROS1, KRAS, BRAF) were observed. The most common platinum doublet administered in first line setting was cisplatin plus pemetrexed. Group A received more frequently carboplatin plus gemcitabine or vinorelbine. Disease Control Rate (DCR) was 57.9% in p included in group A. No differences in DCR were observed in first line between both groups. Time to progression or death was 9.6 m for gropuo B(5-18.1) vs 20.5 m (14.6-37.3) p <0,001 for p in group A.
Conclusion
Rechallenge with platinum-based CT doublets could represent an option for NSCLC p with good PS and no contraindications for such therapy.
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EP1.04 - Immuno-oncology (ID 194)
- Event: WCLC 2019
- Type: E-Poster Viewing in the Exhibit Hall
- Track: Immuno-oncology
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
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EP1.04-25 - Increased PD-L1 Expression in MET Amplified (AMP) Advanced Non Small Cell Lung Cancer (NSCLC) Patients (P) (ID 2764)
08:00 - 18:00 | Author(s): Teresa Moran
- Abstract
Background
MET amp has been reported in a subset of NSCLC p and treatment with crizotinib has proved clinical activity in cases of MET exon 14 alterations and MET amp.. Recently, immunotherapy has emerged as a new approach to treat NSCLC. The development and success of programmed cell death 1 (PD-1)/program death-ligand 1 (PD-L1) checkpoint inhibitors has been correlated with PD-L1 status, particularly in NSCLC p whose tumors express high PD-L1 levels by tumor proportion score (TPS) ⩾ 50%. In this study we have reviewed the PD-L1 status in a cohort of advanced NSCLC p with a METamp.
Method
PDL1 expression has been evaluated in a retrospective cohort of NSCLC p with MET amp and wild type for EGFR, KRAS, BRAF mutations and ALK and ROS1 rearrangements. Overall Survival (OS) was evaluated with Kaplan-Meier curves and groups were compared using log-rank test. Clinical and tumor characteristics, as well as treatment details, were evaluated. MET amp was analyzed by FISH, while PD-L1 status was assessed by immunochemistry by SP 263. antiboby
Result
A total of 50 p were included, 15 p has high or intermediate Met amp and 35 p had low or negative Met amp. Median age were 66 years old. 39 (78%) p were male, 43 (86%) p were smokers or former smokers, 37 p (74%) were ECOG PS 0-1, 37 p (74%) were stage IV. PD-L1 were negative ( < 1%) in 21 p (42%), positive ( >1%) in 26 p ( 52%). PD-L1 highly positive in 18 p ( 36%). Statistically significant more p had PD-L1 positive ( TPS > 1%) in high or intermediate Met amp p versus low or negative ( 92.9% vs 39.4%; p 0.001). And high or intermediate Met amp p had PD-L1 high expression ( TPS > 50%) than negative or low Met amp p ( 64.3% vs 27.3%; p 0.020). No differences in PD-L1 expression was observed by gender, ECOG PS or smoking status. Median OS was 16.367 m (2.295-30.438). No differences in OS were seen by PD-L1 expression or Met amp status.
Conclusion
PD-L1 expression in NSCLC p is positively correlated with MET amp, especially in p with PD-L1 > 50%. Our data suggests that MET amp may play a direct role in up-regulating PD-L1 expression in NSCLC p. Additionally, combination therapy targeting MET and checkpoint inhibition should be considered as a potential therapeutic strategy for NSCLC p with high and intemediate MET amp.
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EP1.16 - Treatment in the Real World - Support, Survivorship, Systems Research (ID 206)
- Event: WCLC 2019
- Type: E-Poster Viewing in the Exhibit Hall
- Track: Treatment in the Real World - Support, Survivorship, Systems Research
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
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EP1.16-17 - Management of Inappropriate Use of Opioids (IUO) in Patients (P) with Lung Cancer (LC) (Now Available) (ID 612)
08:00 - 18:00 | Presenting Author(s): Teresa Moran
- Abstract
Background
Pain represents one of the main symptoms in patients (p) with lung cancer (LC). Currently, the molecular classification and targeted therapies and immunotherapy for LCp yield a prolonged survival in some p. In this context, analgesia with opioid therapy (OT) requires special caution. The prevalence of IUO LCp is unknown and its assessment is suboptimal. There is no current recommendation to assess IUO risk in cancer p, other than in long cancer survivors with chronic pain. Several scales are validated for the screening of aberrant OT-behaviors. The Addiction Unit (AU) role could be key in the evaluation and minimization of the IUO risk (Fig.1)
STUDY DESIGN:Prospective study for the evaluation of IUO risk in LCp. P with intermediate/high risk of IUO will be referred to the AU for evaluation and follow-up (Fig.1)
OBJECTIVES:Determine if screening scales are capable of detecting the risk of IUO in LCp. Reduce the impact of IUO in LCp by assessment and follow-up in the AU.
VARIABLES: Main: To determine if the Cut down-Annoyed-Guilty-Eye opener (CAGE-AD) and Opioid Risk Tool (ORT) scales are able of detecting the risk of IUO in LCp. Secondary: Determine if the urine and blood drug testing (DT) reinforces the information of such scales. Determine the risk reduction of IUO after the intervention of the AU.
Method
ELIGIBILITY CRITERIA (Fig.1)
SCALES:The MO team will use the following scales for the IUO risk assessment: CAGE-AID, ORT. Visual Analogic Scale (VAS) and Edmonton Symptom Assessment Scale (ESAS) will be used for pain evaluation. LABORATORY: DT (urine/ blood ethanol)
ASSESSMENT OF IUO RISK: Proposed timeline and strategies at the AU are summarized in Fig.1.
SAMPLE SIZE:Study will include 45 p in a 1-year period.
Approved by IRB-Hospital Germans Trias in Pujol, Nov, 23th2018 (UIO-pulmon 2018)
Result
Section not applicable
Conclusion
Section not applicable
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MA02 - Miscellaneous Topics in the Management of Early Stage Lung Cancer (ID 116)
- Event: WCLC 2019
- Type: Mini Oral Session
- Track: Treatment of Early Stage/Localized Disease
- Presentations: 1
- Now Available
- Moderators:Mireia Serra-Mitjans, Thomas A. D'Amico
- Coordinates: 9/08/2019, 10:30 - 12:00, Interlaken (1988)
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MA02.01 - Reccurrence Pattern After Adjuvant Customized Chemotherapy Based on BRCA Expression Level (SCAT Trial) (Now Available) (ID 2760)
10:30 - 12:00 | Author(s): Teresa Moran
- Abstract
- Presentation
Background
•Postop platinum-based CT improves outcomes in completely resected NSCLC with nodal involvement, (St II-IIIA). Customization is feasible in adjuvant setting (tissue availability) . Analysis of expressionin genes involved in DNA repair could be use to select CT regiment. •BRCA1 plays an important role in DNA repair pathways and functions as a differential regulator of response to cisplatin and antimicrotubuleagents. SCAT trial results found that for low BRCA1 levels subgroup Cis-Gemcitabine was superior to Cis-Docetaxel and in high BRCA1 levels subgroup Docetaxel single agent without platinum achieved similar survival to Cis-Doc. Analysis of recurrence pattern in different subgroups of the trials has been performed
Method
From Jun/2007 to May/2013 591 patients were screened and 500 p were included (108 in Control arm treated with Cisplatin-Docetaxel and 392 in Experimental arm treated with Cisplatin-Gemcitabine, Cisplatin-Docetaxel or Docetaxel alone according terciles BRCA1 expression level). With a cut-off September 30th 2018 and a median follow-up of 60 months, recurrence pattern are analysed in each arm and subgroup treatment and comparison are made for incidence of risk of recurrence, single/multiple recurrence, thoracic/extrathoracic and site of metastases (liver, bone, brain)
Result
Cumulative recurrence 232/456 evaluable patients (p) (50.8%). Recurrence were seen in 182/354 patients treated in experimental arm and in 50/102 p treated in the control arm (RR 1.04; 0.83-1.30) (p=0.672). Majority of recurrences 159/232 (68.5%) were single site recurrence. Intrathoracic recurrences in 121/232 (52%) while extrathoracic metastatic disease 111/232 (47.8%). No significant differences were seen for single/multiple, intra/extrathoracic recurrences between experimental and control arm. More frequent distant metastatic sites were: bone (42 p), brain (38 p) and liver (11 p) In the experimental group between different treatments no significant differences were found for the overall metastatic rate or for the single/multiple, intrathoracic/extrathoracic recurrences. For specific metastatic sites related to experimental treatment a significant reduction of risk of brain metastases were found in the experimental group with high level BRCA1 treated with Docetaxel single agent (p=0.0016)
Conclusion
For NSCLC resected patients with lymph node involvement (Stages II-IIIA) risk of recurrence remains high with cumulative rate > 50%. There were no differences in the Relative Risk (1.04) of recurrence when control and experimental arm are compared. Majority of recurrences were single site (68.5%) and intrathoracic (52%) but distant metastases developed in 47.8% os p. More frequent metastatic site was bone, followed by brain and liver. Brain metastases risk were significant lower for patients with low BRCA1 expression treated with single agent Docetaxel
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P1.01 - Advanced NSCLC (ID 158)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Advanced NSCLC
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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P1.01-54 - Somatic Genome Alterations in Lung Cancer Patients Diagnosed with Li Fraumeni Syndrome (Now Available) (ID 1014)
09:45 - 18:00 | Author(s): Teresa Moran
- Abstract
Background
Li-Fraumeni syndrome (LFS) is a rare hereditary condition that consists of TP53 mutations inherited in autosomal dominant manner that confer high risk of developing cancer, including lung adenocarcinoma (LUAD). EGFR-mutated LUAD were reported in the context of LFS but there is no systematic description of somatic mutations and characteristics of lung cancer (LC) patients with LFS.
Method
We present a retrospective analysis of clinical and molecular characteristics of patients with LFS diagnosed with LC at the Catalan Institute of Oncology from 1999 to 2019. We collected demographical and clinicopathological features, germline and somatic mutational alterations, treatment and progression-free survival (PFS) and overall survival (OS).
Result
A total of 7 patients with LC and LFS were identified in the Genetic Counseling Unit database. They were carriers of germline mutations in TP53. Five of them were classified as pathogenic: c.638G>A; p.(Arg213Gln), c.725G>A; p.(Cys242Tyr), c.742C>T; p.(Arg248Trp), c.844C>T; p.(Arg282Trp) and c.1010G>A; p.(Arg337His) and two of them as likely pathogenic: c.374C>T; p.(Thr125Met) and c.473G>A; p.(Arg158His). Six out of 7 patients were female and 5 out of 7 never smoker. Median age at diagnosis was 38 year-old (range: 29-74). Five patients had stage IV at diagnosis and the most common histologic subtype was LUAD (5). Six patients had first grade family history of cancer with a median of 2 family members (range: 1-4) and 2 patients had prior history of cancer. Tumor somatic profile in LC was obtained in 6 patients, consisting on a ROS-1 rearrangement in one patient and EGFR mutations in 5 patients (exon 19 deletion in 3 patients and missense mutations in 2 patients, p.(Gly719Ala) at exon 18 and p.(Leu858Arg) at exon 21) and in 1 patient was unknown. All patients with mutant EGFR received EGFR tyrosine kinase inhibitors (TKI) with a median PFS of 29 months (95% CI 0-67). Four had partial response and one a complete response to TKI treatment. At disease progression, one patient had small cell transformation and another acquired EGFR T790M mutation. Median lines of treatment were 4 (range 1-6). Two patients are alive at data cut off. Median OS is 47 months (95% CI 32-62).
Conclusion
Patients diagnosed with LC and LFS are enriched with actionable genomic alterations and have an earlier onset of the disease. Clinical outcome of patients with EGFR mutations and LFS did not differ from EGFR mutated LC patients who do not carry TP53 germline mutations.
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P1.16 - Treatment in the Real World - Support, Survivorship, Systems Research (ID 186)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Treatment in the Real World - Support, Survivorship, Systems Research
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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P1.16-44 - Multiple Primary Cancers (MPC) in a Cohort of Lung Cancer (LC) Patients (P): Incidence and Clinical Features (ID 2236)
09:45 - 18:00 | Author(s): Teresa Moran
- Abstract
Background
The prognosis of p with LC has drastically changed during the last decade due to the improvement in prevention, diagnosis and treatment. Therefore, the number of LC survivor ps has significantly increased and subsequently the incidence of MPC is also rising. This study investigates the co-occurrence of MPC among p diagnosed with LC.
Method
We reviewed of clinical data of patients with histologically confirmed LC visited at our institution between February 2016 and December 2018.
Result
A total of 492 p out of 777 p, (63.3%) had adenocarcinoma and 223 p (28.7%) had squamous LC. The most frequently related comorbidities were hypertension (42.5%), dyslipidemia (36.2%), COPD (21%), cardiovascular disease (15.7%) and diabetes mellitus (14.5%). Molecular analysis was perform in 402 p (51.7%). EGFR mutation was detected in 77 p (exon 19 in 14% and exon 21 in 5% of p). ALK and ROS1 translocation were diagnosed in 27 and 7 p, respectively.
Two primary cancers occurred in 111 cases (14%), including 15 p (1.9%) with three or more primary cancers. Patients with MPC were predominantly males (76.8%), smokers (85%) and 34% had prior family history of MPC. Median age at the first tumor diagnosis was 64 years (57-71). LC occurred as first neoplasm in 8.1% of the cases, 92 p (83%) developed metachronic MPC and 19 p (17%) synchronous MPC. Most common secondary primary cancer were head and neck in 19%, non-melanoma skin cancer in 19%, prostate in 12.6%, bladder and upper urinary tract cancer in 10%, colorectal in 6.3% and breast in 5.4%.
First-line treatment for advanced or locally advance LC included chemotherapy in 65.6%, concomitant chemoradiotherapy in 14%, targeted therapy in 4% and immunotherapy in 4%. Overall response rate (ORR) to first-line treatment was 43.7%. Second-line treatment included chemotherapy in 47.6% and immunotherapy in 30.4%, with and ORR of 30%.
Conclusion
In our series, the frequency of the co-occurrence of MPC among LC p is 14%, suggesting that surveillance strategies are recommended in this population. Most frequent MPC in LC patients are related to smoking. ORR in first and second-line are consistent with the literature.
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P2.05 - Interventional Diagnostic/Pulmonology (ID 168)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Interventional Diagnostics/Pulmonology
- Presentations: 2
- Now Available
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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P2.05-12 - Analysis of Biomarkers in Lung Cancer in Spain (ID 854)
10:15 - 18:15 | Author(s): Teresa Moran
- Abstract
Background
The analysis of biomarkers in lung cancer (LC) is currently one of the most important care needs, given the importance of their presence in the selection of specific treatments. Our objective was to know the implementation degree of these tests in a large cohort of patients in Spain using the Thoracic Tumor Registry (TTR) of the Grupo Español de Cáncer de Pulmón (Spanish Lung Cancer Group).
Method
The TTR is an observational cohort multicenter study of the LC in Spain. Information on patients (p) enrolled from August 2016 to December 2018. The study is conducted according to the Declaration of Helsinki and approved by the institutional review board of each participating institute. The registry was approved by the Spanish Drug Agency as a non-post-authorization, non-interventional study.
Result
A total of 7,872 patients from 58 Spanish sites were enrolled. Analysis of molecular markers considering all the LC stages: A molecular test, the most frequent being the EGFR test, was performed in 4,456 patients (67.5%). The proportion of biomarker evaluation has varied over time, ranging from 57.9% prior to 2012 up to 73.7% in 2017.
Molecular markers in patients with stage IV. Three thousand four hundred forty-six (3,446) patients (52.2%) had a stage IV on diagnosis. The molecular assessment of some biomarkers reached 81.4% of all the patients, there being differences between Regional Communities in regard to the molecular tests made.
There was performed some biomarker test in 92% of the 2570 patients with stage IV and adenocarcinoma histology. The analysis of ALK was tested in 79% of the patients, this being in 40% only 2 years ago. ROS was studied in 20% of the cases and EGFR in 92%.
Conclusion
Although no national plan exists for molecular biomarker analysis in LC in Spain, the implementation of the biomarkers analysis in all the hospitals that contribute to the TTR is high, as close to the maximum as possible. The increase in the ALK analysis in the last period is relevant. As regional differences exist, it would be of interest to go in depth to study its cause
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P2.05-15 - Radial Endobronchial Ultrasound-Guided Transbronchial Biopsy in Peripheral Lung Lesions. What Can Cryobiopsy Contribute? (Now Available) (ID 865)
10:15 - 18:15 | Author(s): Teresa Moran
- Abstract
Background
Radial probe endobronchial ultrasound (RP-EBUS) is a modern technique for diagnosis of peripheral lung lesions. The addition of transbronchial cryobiopsy (TBCB) could increase the diagnostic value for RP-EBUS. AIM: To evaluate the efficacy of RP-EBUS guided TBCB for diagnosis of peripheral lung lesions.
Method
We collected 60 patients with peripheral lung diseases. Were excluded 15 patients for not be fit for general anesthesia (necessary for TBCB) or high risk of bleeding. 45 patients were subjected to forceps transbronchial biopsy (forceps TBB) and TBCB guided by RP-EBUS. The diagnostic outcomes including digital assessment for qualitative and quantitative measures of collected samples were detected. Also, the associated complications were recorded.
Result
The diagnostic yields for forceps TBB versus TBCB is detailed in Table 1. TBCB has achieved higher accuracy than forceps TBB (ROC area of 0.88 versus 0.84 respectively), with no statistical difference between their values (p=0.32). The combination between both techniques has achieved excellent accuracy (ROC area 0.91). In 36 cases were possible the anatomopathological diagnosis with both type of samples, there were significant statistical differences (p ≤ 0.05) in favour of TBCB when compared to forcep TBB regarding; mean biopsy diameter, mean biopsy surface area, mean biopsy necrosis, percentage and mean biopsy viable tissue area. Only two patients had significant complications (pneumothorax; hypoxemia), and 8 moderate bleeding.
Conclusion
Conclusions: RP-EBUS guided TBCB is a safe and effective technique for diagnosis of peripheral lung lesions. TBCB could achieve higher diagnostic value than forceps TBB due to better quantity and quality of the samples.
The project was partially funded by SEPAR, grant AEER 2016, grant FUCAP 2017 and Egyptian Ministry of Higher Education.
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P2.13 - Staging (ID 315)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Staging
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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P2.13-05 - Endobronchial Ultrasound for Mediastinal Restaging in Non-Small Cell Lung Cancer (Now Available) (ID 858)
10:15 - 18:15 | Author(s): Teresa Moran
- Abstract
Background
The adequate mediastinal restaging following neo-adjuvant therapy (NAT) in operable patients with non-small cell lung cancer (NSCLC) and N2 spread is crucial. Mediastinoscopy is the gold standard for mediastinal restanging, but endosonographic procedures are less invasive and can be an alternative. AIM: Evaluate the role of endobronchial ultrasound-guided transbronchial needle aspirate EBUS-TBNA in mediastinal the restaging of NSCLC.
Method
Prospective study with 32 patients with CPNCP N2 spread confirmed by TNBA-EBUS, collected from June 2010 to October 2018. These patients were subjected to neoadjuvant treatment (chemotherapy or radio-chemotherapy), subsequently were performed mediastinum restage with TNBA-EBUS. The negative cases were subjected to mediastinoscopy or thoracotomy.
Result
Of the 32 cases, the basal characteristics are detailed in table 1. Were analysed 229 lymph nodes, 42 of these were malignant (18%). TNBA-EBUS after neoadjuvant treatment showed persistence of N2 spread in 19 cases (52%). In negative cases (n=13; 41%) were performed mediastinoscopy (n=11) or surgery (n=1). After these procedures were confirmed mediastinal disease in 3 cases, 9 lymph nodes of 43 removed. The sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy were 86.4%, 100%, 100%, 72.7% and 90% respectively. There was recurrence of the disease in 15 cases (47%). We found a significant difference between recurrence and the type of neoadjuvant treatment (chemotherapy vs. radio-chemotherapy), p=0.047.
Table 1.
Conclusion
TBNA-EBUS is an appropriate semi-invasive tool in mediastinal restage after neoadjuvant treatment, with high diagnostic accuracy. Nevertheless, in negative cases is still necessary support with invasive procedures.
