995P Effectiveness of combination of osimertinib with another targeted therapy in advanced EGFR mutated non-small cell lung cancer harbouring other oncogenic drivers: The real-world COMPOSIT study

Abstract

Identification of resistance mechanisms is crucial to guide therapeutic approaches in patients receiving osimertinib (O). The COMPOSIT study is a French national cohort reporting the effectiveness and tolerance of O in combination with another targeted therapy (TT) in patients with advanced EGFR mutated NSCLC harboring other oncogenic drivers. Patients (pts) treated with O between 01.01.2017 and 30.04.2021 who received a combination of O with another TT were included. Clinical pathological and molecular data were retrospectively collected. The primary endpoint was real-world progression free survival (rwPFS). 55 pts were included from 14 centers. Median age was 59 years (range 29-83); 56.3% were women, 60% never smokers and DelEx19 of EGFR was observed in 69% of cases. Combination therapy was administered to 23 pts who received O as 1st line (41.8%) and to 32 pts in whom O was administrated after receiving chemotherapy and/or 1st or 2nd generation EGFR TT (58.2%). MET pathway was the most targeted mechanism by combination therapies (66.1%). Real world PFS data was available for 54 combinations. Median follow-up was 16.7 months (95% CI; 13.3-19.1). The median rwPFS was 4.1 months (95% CI; 3.2-5.5). Overall response rate (ORR) was 49.0% (95% CI; 35.3-62.7%). The median overall survival (OS) was 11.9 months (95% CI; 8.6-19.6). In MET pathway alterations, rwPFS was 5.3 months (95 CI; 3.9-6.7), ORR 59.4% (95% CI; 42.4-76.4) and OS 14.8 months (95% CI; 7.4-33.2). Adverse events (AE) of grade >2 were reported in 13 patients (23.6%), mainly not related to O (93%). The frequency of drug interruption due to AE was 12.7%.Table: 995PCombination therapies with osimertinib (O) evaluated in COMPOSIT StudyPatients (n=55)Alteration targetedO + Targeted therapy36MET amplificationO + crizotinib (n=19) O + capmatinib (n=7) O + savolitinib (n=4) O + tepotinib (n=5) O + crizotinib then O + capmatinib (n=1)5BRAF fusionO + trametinib5BRAF V600EO + trametinib (n=1) O + dabrafenib (n=2) O + dabrafenib Trametinib (n=2)2EGFR C797S + T790MO + brigatinib1EGFR C797S + T790M cisO + gefitinib1EGFR L861Q + G724S + T790MO + afatinib2RET rearrangementO + praseltinib1ALK rearrangementO + crizotinib1FGFR1 amplificationO + erdafitinib1HER2 amplificationO + trastuzumab Open table in a new tab To our knowledge, this is the largest real-world study of combination therapies in patients with advanced EGFR-mutated NSCLC harboring other oncogenic drivers. Combination approaches with O are already used to overcome resistance by clinicians.