1388P - Real-world prognostic value of RET fusions in advanced non-small cell lung cancer (aNSCLC)

Background

RET fusions are found in 1–2% of patients (pts) with NSCLC. RET inhibitors (RETi) have recently been approved for RET fusion-positive (RET+) aNSCLC, but the prognostic value of RET fusions is unclear. This study aimed to describe the overall survival (OS) of pts with RET+ or RET wild-type (RET-WT: no RET alterations) NSCLC using real-world data from two large databases.

Methods

This was a retrospective, observational study using US-based data from 1) a nationwide Flatiron Health–Foundation Medicine NSCLC clinico-genomic de-identified database (FH-FMI CGDB) and 2) a nationwide longitudinal electronic health record-derived FH de-identified database (FH). Pts with aNSCLC diagnosed between 1 Jan 2011 and 31 Dec 2021 (CGDB) or 30 Sep 2022 (FH) with known RET fusion status were included. Pts with other actionable gene alterations or previous treatment with RETi or a clinical study drug in any line were excluded. The primary objective was to compare the OS of pts with RET-WT vs RET+ aNSCLC in 1) all pts (index date: date of advanced diagnosis) and 2) pts who received first-line (1L) chemotherapy plus cancer immunotherapy (index date: start of 1L therapy). Hazard ratios (HRs) for left-truncated OS (to account for immortal time from index to RET testing) were adjusted for confounding variables using a multivariate Cox proportional regression model.

Results

Overall, 45 (CGDB) and 60 (FH) pts with RET+ aNSCLC, and 5,890 (CGDB) and 16,566 (FH) pts with RET-WT aNSCLC were included in the analysis. Pts with RET+ NSCLC tended to be younger (<65 yrs old: 51% vs 33%), less frequently smokers (8% vs 47%), and less commonly had KRAS (7% vs 34%) and TP53 (42% vs 72%) mutations than RET-WT pts. In CGDB and FH, there was no significant difference in OS between RET-WT and RET+ pts (Table).

Conclusions

Data from this real-world study using two large databases show that pts with RET+ aNSCLC do not have a different prognosis than pts with RET-WT aNSCLC. These data suggest that RET fusions have no prognostic value in aNSCLC. Table: 1388P

*Index: advanced diagnosis date; ^†index: start of 1L therapy; ^‡ adjusted by multivariate Cox proportional regression model for multiple covariates.

Clinical trial identification

Editorial acknowledgement

Medical writing support for the development of this abstract was provided by Lietta Nicolaides, PhD, and Laura Vergoz, PhD, of Ashfield MedComms, an Inizio company, and funded by F. Hoffmann-La Roche Ltd.

Legal entity responsible for the study

F. Hoffmann-La Roche Ltd/Genentech, Inc.

Funding

F. Hoffmann-La Roche Ltd/Genentech Inc.

Disclosure

S.M. Gadgeel: Financial Interests, Personal, Advisory Board: Genentech/Roche, AstraZeneca, Mirati, Pfizer, Blueprint, Takeda, Bristol Myers Squibb, Merck, Eisai, Gilead, GSK, Arcus; Financial Interests, Personal, Other, Travel: Mirati. Q. Zhang: Financial Interests, Personal, Full or part-time Employment: Roche/Genentech; Financial Interests, Personal, Stocks/Shares: Roche, Regeneron, BMS, AbbVie, Pfizer, BioNTech, AC Immune. O. Fajardo: Financial Interests, Personal, Full or part-time Employment: F. Hoffmann-La Roche; Financial Interests, Personal, Stocks/Shares: F. Hoffmann-La Roche. H. Trinh: Financial Interests, Personal, Full or part-time Employment: Genentech, Inc; Financial Interests, Personal, Stocks/Shares: Roche. S. Kong: Financial Interests, Personal, Other, Former Employee: Roche; Financial Interests, Personal, Stocks/Shares: Roche. A. Rahman: Financial Interests, Personal, Stocks/Shares: Merck, Roche; Financial Interests, Personal, Full or part-time Employment: Roche. S. Li: Financial Interests, Personal, Full or part-time Employment: Genentech, Inc. V.R. Archer: Financial Interests, Personal, Full or part-time Employment: Roche; Financial Interests, Personal, Stocks/Shares: Roche. J.F. Gainor: Financial Interests, Personal, Advisory Board: AI Protein, AstraZeneca, BeiGene, Bristol Myers Squibb, Genentech/Roche, GlydeBio, iTeos, Karyopharm, Lilly, Merck, Mirati, Moderna, Novartis, Pfizer, Silverback Therapeutics, Takeda; Financial Interests, Personal, Stocks/Shares: Ironwood Pharmaceuticals; Non-Financial Interests, Institutional, Coordinating PI: Alexo, AstraZeneca, Bristol Myers Squibb, Genentech, Inc. Jounce, Merck, Moderna, Novartis; Financial Interests, Personal, Coordinating PI: Novartis; Financial Interests, Personal, Local PI: Scholar Rock and Palleon; Other, Personal, Full or part-time Employment, Immediate family member is an employee: Ironwood Pharmaceuticals. All other authors have declared no conflicts of interest.