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Pieter E. Postmus
MA21 - Non EGFR/MET Targeted Therapies (ID 153)
- Event: WCLC 2019
- Type: Mini Oral Session
- Track: Targeted Therapy
- Presentations: 1
- Now Available
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): Pieter E. Postmus
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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P2.04 - Immuno-oncology (ID 167)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Immuno-oncology
- Presentations: 1
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
P2.04-47 - Tumor Mutational Load, CD8+ T Cells, Expression of PD-L1 and HLA Class I to Guide Immunotherapy Decisions (ID 1259)
10:15 - 18:15 | Author(s): Pieter E. Postmus
A minority of NSCLC patients benefit from anti-PD1 immune checkpoint inhibitor therapy. A rational combination of biomarkers is needed. The value of using a series of mechanism-of-action based parameters was studied for response prediction of immunotherapy: tumor mutational load (TML), CD8+ T cell infiltration, HLA class I expression and the currently used PD-L1 tumor proportion score.Method
Patients were prospectively included between April 2016 and August 2017, and retrospectively analyzed. Metastatic NSCLC patients (n=30) with sufficient archival tissue, obtained prior to the first nivolumab administration, were selected. Response was assessed by RECIST v1.1. Progression-free survival (PFS) and overall survival (OS) were analyzed by Kaplan-Meier methodology. TML was determined using a next-genome sequencing panel (409 cancer-related genes). Immunohistochemistry was performed to score PD-L1, total CD8+ T cell infiltration and HLA class I.Result
In 30 patients with adenocarcinoma (67%) or squamous cell carcinoma (33%), high TML was significantly associated with better PFS (p=0.004) and OS (p=0.025). Interaction analyses revealed that patients with both high TML and high total CD8+ T cell infiltrate (p=0.023) or no loss of HLA class I (p=0.026), patients with high total CD8+ T cell infiltrate and no loss of HLA class I (p=0.041) or patients with both high PD-L1 and high TML (p=0.003) or no loss of HLA class I (p=0.032) were significantly associated with better PFS. Unsupervised cluster analysis based on the four markers revealed three sub-clusters, of which cluster 1A was overrepresented by patients with progressive disease (15 out of 16), with significant effect on PFS (p=0.007).Conclusion
This proof-of-concept study suggests that a combination of PD-L1 expression, TML, CD8+ T cell infiltration and HLA class I expression function as a better predictive biomarker for the response to anti-PD-1 immunotherapy and PFS. Consequently, refinement of this proposed set of biomarkers and validation in a larger set of patients is warranted.