1294P - Non-adenocarcinoma histology in patients with RET+ lung cancer: Response to RET-inhibitors and survival from the RET-MAP registry

Background

RET fusions are present in 1-2% of lung cancer cases, primarily in patients (pts) with adenocarcinoma (LUAD). Despite their presence in some non-adenocarcinoma lung cancers (non-LUAD), RET status is not routinely assessed in these pts. The impact of non-LUAD histology on treatment outcomes and prognosis in RET+ lung cancer remains largely unreported due to their rarity.

Methods

We performed a multicentric retrospective study, including pts with RET+ lung cancer, treated or not with RET inhibitors (RETi) in 38 international centers. We compared clinical and biological features, best response rates, and survival outcomes of pts with LUAD versus non-LUAD. Progression-free survival (PFS) and overall survival (OS) were assessed from date of treatment start.

Results

Out of 369 pts with RET+ lung cancer, 25 (7%) had non-LUAD (8 large cell neuroendocrine, 6 undifferentiated, 4 squamous, 2 sarcomatoid, 2 adenosquamous, 1 small cell carcinoma, 3 other subtypes). Median age was 62 years, 55% were female, 40% were smokers, 22% had brain metastases (BM), median PD-L1 expression was 10% (0-55). No differences in sex, age, smoking, PD-L1 expression, or fusion partner were observed between LUAD and non-LUAD. 251 pts received a RETi, of whom 14 had non-LUAD and 237 LUAD. At RETi start, the median number of line was 2 (IQR 1-3), and more non-LUAD pts had BM (50% vs 20%, p=0.015). mPFS and mOS from RETi start were shorter in pts with non-LUAD as compared to LUAD (6.17 vs 16.3 mo, p=0.028, 13.4 vs 29.1 mo, p=0.011, respectively). The majority of pts with non-LUAD showed response to RETi, even if in a lower proportion than LUAD (54% vs 72.1%, p=0.04). 239 pts received chemotherapy, 18 with non-LUAD and 221 LUAD. Median number of line was 1 (IQR 1-2). mPFS and mOS from chemotherapy start were shorter in non-LUAD (5.23 vs 9.17 mo, p=0.022, 11.3 vs 38.1 mo, p=0.02, respectively), and response rates were 29% vs 43% in non-LUAD vs LUAD (p=0.3).

Conclusions

Nearly 7% of patients with RET+ lung cancer have non-LUAD histology. This subgroup exhibits a poorer prognosis and shorter outcomes under RETi or chemotherapy. However, a response to RETi is observed in more than half of cases, justifying molecular testing.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Mihaela Aldea.

Funding

Has not received any funding.

Disclosure

J. Rotow: Financial Interests, Personal, Advisory Role: AstraZeneca, Janssen, Guardant, Genentech. F. Guisier: Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, BMS, MSD, Roche, Sanofi, Janssen, Pfizer, Takeda; Financial Interests, Institutional, Research Grant: Pfizer, Roche, Takeda. M. Duruisseaux: Financial Interests, Personal, Advisory Board: Roche, BMS, Nanostring, MSD, AstraZeneca, AbbVie, Takeda, Boehringer Ingelheim, Blueprint, Merus, and Pfizer; Financial Interests, Personal, Speaker, Consultant, Advisor: Roche, BMS, MSD, AstraZeneca, AbbVie, Takeda, Boehringer Ingelheim, and Pfizer; Financial Interests, Personal and Institutional, Sponsor/Funding: Novartis, Nanostring, and Blueprint. J. Raimbourg: Financial Interests, Institutional, Invited Speaker: AstraZeneca, Pierre Fabre, Amgen, Sanofi; Financial Interests, Institutional, Advisory Board: Takeda, BMS, Merck. M. Tagliamento: Non-Financial Interests, Member, International Lung Cancer Foundation Fellow: IASLC; Non-Financial Interests, Member, Lung Cancer Group: EORTC; Other, Travel and accommodation expenses: Eli Lilly. J. Feng: Financial Interests, Personal, Invited Speaker: AstraZeneca. A. Di Federico: Financial Interests, Personal, Advisory Board: Hanson-Wade; Financial Interests, Personal, Other: SITC. F. Tabbò: Financial Interests, Personal, Speaker, Consultant, Advisor: Roche, AstraZeneca, Takeda. C. Lindsay: Financial Interests, Personal, Invited Speaker, Advisory role: Amgen; Financial Interests, Personal, Invited Speaker, Educational Presentation/Workshop: Amgen; Financial Interests, Personal, Advisory Board: Qiagen; Financial Interests, Institutional, Coordinating PI, CI for a phase III clinical trial: Mirati Therapeutics, Amgen; Financial Interests, Institutional, Coordinating PI, CI for a phase I-II clinical trial: BI, Revolution Medicines; Financial Interests, Institutional, Coordinating PI, CI for a phase II clinical trial: Roche; Financial Interests, Institutional, Local PI, PI for a phase II clinical trial: Apollomics; Financial Interests, Institutional, Research Grant, Research funding which includes use of their medical products: Revolution Medicines; Non-Financial Interests, Personal, Other, Travel funding for poster presentation: Boehringer Ingelheim; Other, Review paper co-oordinated by Amgen. Initially drafted by other writers, with contributions from co-authors.: Amgen. P. Iranzo Gomez: Financial Interests, Personal, Speaker, Consultant, Advisor: Bristol Myers Squibb, F. Hoffemann, La Roche AG, Boehringer Ingelheim, MSD, Rovi, Yowa Kirin, Grunenthal Pharma S.A, Pfizer, Medscape, Kern Pharma. B. Besse: Financial Interests, Institutional, Advisory Board: Amgen, AstraZeneca, BeiGene, Blueprint Medicine, Cergentis, Chugai pharmaceutical, Daiichi Sankyo, F. Hoffmann-La Roche, Inivata, Pfizer, PharmaMar, Sanofi Aventis, Springer Healthcare Ltd., 4D Pharma, AbbVie, Da voltera, Eli Lilly, Ellipse pharma Ltd., F-Star, GSK, Janssen, Onxeo, OSE Immunotherapeutics, Socar research, Taiho Oncology, Turning Point Therapeutics; Financial Interests, Institutional, Invited Speaker: Genzyme Corporation, Hedera Dx, Medscape, MSD; Financial Interests, Institutional, Local PI: AbbVie, Amgen, Blueprint Medicines, Daiichi Sankyo, Pfizer, Roche-Genentech, Turning Point Therapeutics, Nuvalent, Enliven, Prelude therapeutics; Financial Interests, Institutional, Coordinating PI: AstraZeneca, OSE Immunotherapeutics, Sanofi, Taiho; Financial Interests, Institutional, Steering Committee Member: BeiGene, GSK, Janssen, Takeda, Genmab; Financial Interests, Institutional, Funding: Cristal Therapeutics. M. Aldea: Financial Interests, Personal, Other: Sandoz; Financial Interests, Personal and Institutional, Research Grant: Sandoz; Financial Interests, Personal, Advisory Role: Viatris. All other authors have declared no conflicts of interest.