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P. Fidias
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MINI 25 - Trials, Radiation and Other (ID 142)
- Event: WCLC 2015
- Type: Mini Oral
- Track: Thymoma, Mesothelioma and Other Thoracic Malignancies
- Presentations: 1
- Moderators:J.M. Clavero, R. Hassan
- Coordinates: 9/08/2015, 16:45 - 18:15, 702+704+706
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MINI25.04 - Utilizing Molecular Profiling to Identify Potential Therapies in Sarcomatoid Lung Cancer (ID 655)
17:00 - 17:05 | Author(s): P. Fidias
- Abstract
- Presentation
Background:
Sarcomatoid lung cancer (SLC) is an aggressive subset of poorly differentiated non-small cell lung carcinoma (NSCLC), comprising just one percent of all NSCLC. Further elucidation of this unique histological entity has been hampered by a lack of large-scale clinical trial evidence. The National Comprehensive Cancer Network (NCCN) contains no clear direction regarding optimal management. The purpose of this study, therefore, is to identify potential therapeutic options for this disease using a multiplatform, biomarker-directed approach.
Methods:
In total, 48 SLC specimens analyzed via a multiplatform profiling service (Caris Life Sciences, Phoenix, AZ) consisting of gene sequencing (Sanger or next generation sequencing [NGS]), protein expression (immunohistochemistry [IHC]) and gene amplification (CISH or FISH) were retrospectively evaluated.
Results:
High rates of PD-L1 (83.3%, 5/6) and PD-1 (80.0%, 4/5) protein expression by IHC imply benefit to recently-approved compounds. EGFR amplification by ISH (18.8%, 3/16) and MET amplification (9.5%, 2/21) were independent of EGFR mutation in this group. No ALK, HER2 or ROS1 ISH abnormalities were detected. Mutational analysis shows the highest mutation rates in TP53 (50.0%, 7/14), KRAS (44.4%, 16/36), cKIT (5.3%, 1/19), EGFR (5.1%, 2/39) and BRAF (4.8%, 1/21). The two EGFR mutations detected were L858R and exon 20 insertion.
Conclusion:
Multiplatform profiling identified multiple potential actionable targets with various approved therapies. PD-1 and PD-L1 overexpression rate was comparable to that published in sarcomatoid renal cell carcinoma. Therefore, new immunotherapies should be prospectively tested in sarcomatoid disease specific trials based on high PD-1/PD-L1 overexpression. Our finding of low EGFR mutational frequency is consistent with previous, published findings in this disease. Lower rates of ALK, ROS1, and EGFR are not surprising given SLC’s association with smoking. Clinical trials evaluating the benefit of imatinib and vemurafenib in subgroups with cKIT or BRAF mutations may be worthwhile.
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ORAL 16 - Clinical Care of Lung Cancer and Advanced Biopsies (ID 115)
- Event: WCLC 2015
- Type: Oral Session
- Track: Treatment of Advanced Diseases - NSCLC
- Presentations: 1
- Moderators:J.W. Neal, Q. Zhou
- Coordinates: 9/08/2015, 10:45 - 12:15, Mile High Ballroom 2a-3b
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ORAL16.03 - Acceptability of NSCLC, NOS in Advanced Disease: An Assessment of US Oncologists, Pulmonologists and Pathologists (ID 1255)
11:07 - 11:18 | Author(s): P. Fidias
- Abstract
- Presentation
Background:
In 2011 the College of American Pathologists, the International Association for the Study of Lung Cancer, and the Association for Molecular Pathology issued a recommendation to classify patients with advanced NSCLC into specific histological and molecular subtypes and minimize the diagnosis of not otherwise specified (NOS) subtype. The objective of this study was to define the rate of NOS subtype being observed in practice as well as the NSCLC care team’s knowledge and beliefs about a diagnosis of NOS subtype in advanced-stage disease.
Methods:
A series of 5 questions were developed to identify the incidence of NOS subtype being observed in the community as well as relevant care team knowledge gaps and beliefs that may influence the findings. The case vignettes and questions and were based on current standards of care and evidence-base in the treatment of advanced NSCLC. The questions were made available online to healthcare providers either through a survey or as part of 2 certified medical education activities; without monetary compensation or charge. Confidentiality of survey respondents was maintained and responses were de-identified and aggregated prior to analyses. The series of 5 questions was launched in both formats in December 2014 and participant responses were collected over the following 4 months.
Results:
In total, 553 oncologists, pathologists and pulmonologists answered all 5 questions. Oncologists who responded to the questions on average saw about 6-10 patients with suspected or diagnosed NSCLC per month while pathologists and pulmonologists were more likely to see 1-5 per month. Almost 60% of oncologists, pathologists and pulmonologists stated that the incidence of NOS subtype should occur in less than 5% of all cases. Yet, 28% of participating oncologists, 37% of pathologists, and 40% of pulmonologists would find a diagnosis of NSCLC, NOS acceptable. Moreover, 45% of oncologists and 64% of pulmonologists stated that 11% or more of their patients are reported as having a diagnosis of NSCLC, NOS. Reasons for acceptability of NOS subtype differed between clinicians; with more pulmonologists stating it is always acceptable while pathologists and oncologists were more likely to cite age or smoking status, respectively. When asked what contributes to this belief a majority of oncologists and pathologists cited an inability to obtain adequate tissue while pulmonologists were more likely to state that subtyping was unnecessary to prescribe the appropriate therapy (30%) or it was a result of system barriers (25%).
Conclusion:
Despite recommendations from key organizations the incidence of NSCLC, NOS many members of the care team continue to accept a diagnosis of NOS in their patients. Our findings demonstrate a pressing need for additional education of the multidisciplinary care team involved in the diagnosis of advanced NSCLC so as to ensure appropriate diagnosis and treatment.
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