2356P - The role of pathological features in predicting prognosis of patients with advanced RET-positive NSCLC

Background

RET fusions are observed in 1-2% of patients (pts) with non-small cell lung cancer (NSCLC). Targeted therapies with RET inhibitors (RETi) have proven efficacy, improving survival, whereas data on immune checkpoint inhibitors (ICI) are controversial. Aim of the study was to evaluate if pathologic features could have a role as prognostic markers for RET+ NSCLC.

Methods

In this multicentric observational study of 5 European centers baseline tissue specimens were collected from pts with advanced RET+ NSCLC. Clinical data and treatment outcomes with RETi and ICI were collected. Overall survival (OS) in the overall population and progression-free survival (PFS) for RETi and ICI in pts treated with RETi and ICI were calculated. Tumor grade, histological subtype, presence of fibrosis, necrosis, tumor infiltrating lymphocytes (TILs), tertiary lymphoid structures (TLs), lymphangitis, calcifications, neutrophils were determined on haematoxylin/eosin (HE) coloured tissue slides for each patient. We investigated whether pathological features were correlated with PFS and OS.

Results

38 pts with advanced NSCLC were included. Median age was 62 (IQR 58-72), 63% were female, median number of metastatic sites was 2 (IQR 1-3), PS ECOG was ≤1 in 92%1, 28 were treated with RETi, 18 received ICI. Median OS was 50.7 months (95%CI 28.4-NA). Necrosis was observed in 20% of pts and it was associated with shorter OS (7.67 vs 61.10 vs months, p<0.001), both in pts treated or untreated with RETi (7.97 vs 83.7 and 4.78 vs 13.93 months, p<0.001). Shorter PFS with RETi (5.23 vs 17.37 months, p=0.004) was also observed in presence of necrosis. Histological subtype (92% adenocarcinoma), tumor grade (50% G3), presence of fibrosis (84%), TILs (28%), TLs (10%), lymphangitis (62%), neutrophils (3%), calcifications (17%) did not seem to have a prognostic value.

Conclusions

The presence of necrosis in baseline histological samples from advanced RET+ NSCLC was associated with worse prognosis in pts treated or note with RETi. The role of pathological features as prognostic biomarkers deserves further investigation in this setting.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Gustave Roussy.

Funding

Has not received any funding.

Disclosure

A. Russo: Financial Interests, Personal, Advisory Board: AstraZeneca, MSD, Novartis, Pfizer. A. Gazzah: Non-Financial Interests, Institutional, Principal Investigator: AbbVie, Adaptimmune, Adlai Nortye USA Inc., Aduro Biotech, Agios Pharmaceuticals, Amgen, Argen-X Bvba, Arno Therapeutics, Astex Pharmaceuticals, AstraZeneca Ab, Aveo, Basilea Pharmaceutica International Ltd., Bayer Healthcare Ag, Bbb Technologies Bv, Beig; Financial Interests, Personal and Institutional, Research Grant: AstraZeneca, BMS, Boehringer Ingelheim, GSK, INCA, Janssen Cilag, Merck, Novartis, Pfizer, Roche, Sanofi. F. Barlesi: Financial Interests, Institutional, Advisory Board: AstraZeneca, Bayer, Bristol Myers Squibb, Boehringer Ingelheim, Eli Lilly Oncology, F. Hoffmann-La Roche Ltd., Novartis, Merck, Mirati, MSD, Pierre Fabre, Pfizer, Sanofi-Aventis, Seattle Genetics, Takeda, AbbVie, ACEA, Amgen, Eisai, Ignyta; Non-Financial Interests, Principal Investigator: AstraZeneca, BMS, Merck, Pierre Fabre, F. Hoffmann-La Roche Ltd., Innate Pharma, Mirati. J. Remon Masip: Financial Interests, Personal, Invited Speaker: Roche, MSD, Boehringer Ingelheim; Financial Interests, Personal, Writing Engagement: Pfizer; Financial Interests, Personal, Advisory Board: AstraZeneca, OSE Immunotherapeutics, BMS, Janssen, Takeda, Sanofi; Financial Interests, Institutional, Invited Speaker: Merck Portugal; Non-Financial Interests, Principal Investigator, PI of PECATI trial in Thymic malignancies endorsed by a grant by MSD: MSD; Non-Financial Interests, Other, Co-PI of APPLE trial (EORTC-1525): AstraZeneca; Non-Financial Interests, Member, Secretary of the Lung Cancer Group at the EORTC: EORTC. D. Planchard: Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, Merck, Novartis, Pfizer, Roche, Samsung, Celgene, AbbVie, Daiichi Sankyo, Janssen, Seagen, Gilead, Pierre Fabre; Financial Interests, Personal, Invited Speaker: AstraZeneca, Novartis, Pfizer, prIME Oncology, Peer CME, Samsung, AbbVie, Janssen; Non-Financial Interests, Principal Investigator, Institutional financial interests: AstraZeneca, BMS, Merck, Novartis, Pfizer, Roche, Daiichi Sankyo, Sanofi-Aventis, Pierre Fabre; Non-Financial Interests, Principal Investigator: AbbVie, Sanofi, Janssen. B. Besse: Financial Interests, Institutional, Funding: 4D Pharma, AbbVie, Amgen, Aptitude Health, AstraZeneca, BeiGene, Blueprint Medicines, Boehringer Ingelheim, Celgene, Cergentis, Cristal Therapeutics, Daiichi Sankyo, Eli Lilly, GSK, Janssen, Onxeo, OSE immunotherapeutics, Pfizer, Roche-Genentech, Sanofi, Takeda, Tolero Pharmaceuticals; Financial Interests, Institutional, Research Grant: Chugai Pharmaceutical, Eisai, Genzyme Corporation, Inivata, Ipsen, Turning Point Therapeutics. All other authors have declared no conflicts of interest.