Abstract 995P
Background
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.
Methods
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).
Results
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: 995P
Combination therapies with osimertinib (O) evaluated in COMPOSIT Study
| Patients (n=55) | Alteration targeted | O + Targeted therapy |
| 36 | MET amplification | O + crizotinib (n=19) O + capmatinib (n=7) O + savolitinib (n=4) O + tepotinib (n=5) O + crizotinib then O + capmatinib (n=1) |
| 5 | BRAF fusion | O + trametinib |
| 5 | BRAF V600E | O + trametinib (n=1) O + dabrafenib (n=2) O + dabrafenib Trametinib (n=2) |
| 2 | EGFR C797S + T790M | O + brigatinib |
| 1 | EGFR C797S + T790M cis | O + gefitinib |
| 1 | EGFR L861Q + G724S + T790M | O + afatinib |
| 2 | RET rearrangement | O + praseltinib |
| 1 | ALK rearrangement | O + crizotinib |
| 1 | FGFR1 amplification | O + erdafitinib |
| 1 | HER2 amplification | O + trastuzumab |
Conclusions
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.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
A. Swalduz: Financial Interests, Personal, Advisory Board: BMS, AZD, Takeda, Roche, Lilly, Pfizer, Amgen, Janssen; Non-Financial Interests, Principal Investigator: Novartis, Roche, Takeda. I. Monnet: Other, invitation to virtual ASCO 2021 and 2022: Pfizer; Other, invitation to ESMO Congress 2021 and 2022: Takeda. F. Guisier: Financial Interests, Personal, Advisory Board: BMS, AstraZeneca, MSD, Roche, Amgen; Financial Interests, Personal, Invited Speaker: Pfizer, Takeda; Financial Interests, Institutional, Research Grant: Takeda, Pfizer. A. Cortot: Financial Interests, Personal, Advisory Board: Astra-Zeneca, Novartis, Roche, Pfizer, Janssen; Financial Interests, Personal, Invited Speaker: BMS, Astra-Zeneca, MSD, Pfizer, Novartis, Takeda, Roche, Novartis; Financial Interests, Institutional, Research Grant: Merck, Roche; Financial Interests, Institutional, Invited Speaker: Astra-Zeneca, Janssen, Xcovery, Roche, Novartis, Amgen, Mirati; Non-Financial Interests, Invited Speaker: French Thoracic Intergroup. V. Gounant: Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, Takeda. B. Duchemann: Financial Interests, Personal, Expert Testimony: BMS, AstraZeneca, Amgen, Lilly; Financial Interests, Personal, Invited Speaker: ROCHE, Chiesi; Financial Interests, Personal, Other, Congres/travel fees: Oxyvie. E. Giroux-Leprieur: Financial Interests, Personal, Advisory Board: AstraZeneca, Bristol-Myers-Squibb, Boehringer Ingelheim, MSD, Novartis, Janssen, Pfizer, Roche; Financial Interests, Personal, Invited Speaker: Takeda; Non-Financial Interests, Invited Speaker: French Intergroup of Thoracic Oncology IFCT. T. Pierret: Financial Interests, Personal, Invited Speaker: BMS; Financial Interests, Personal, Advisory Board: pfizer. J. Cadranel: Financial Interests, Personal, Advisory Board, Participation to boards: BMS, Jansen, AZ, BI, Takeda, MSD, Novartis, Amgen; Financial Interests, Institutional, Research Grant, Drug and funding for academic trial: Pfizer; Financial Interests, Institutional, Research Grant: AbbVie, Sanofi; Non-Financial Interests, Principal Investigator, Participation to trials: AZ, BI, Amgen, Takeda, MSD, BMS, Novartis, Jansen; Non-Financial Interests, Principal Investigator, Participation to trials and boards: Sanofi. V. Fallet: Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, Takeda, Roche, Pfizer, Sanofi, Sandoz, Jansen; Financial Interests, Personal, Invited Speaker: AstraZeneca, BMS, Takeda, Pfizer, MSD; Financial Interests, Personal, Expert Testimony: GSK, Boehringer. All other authors have declared no conflicts of interest.