Abstract 74P
Background
Clinical trials are now ongoing to evaluate the efficacy and safety of experimental first-line treatment for advanced EGFR-mutated NSCLC, compared to osimertinib monotherapy.
Methods
We performed a systematic reviewof the literature and an IPD meta-analysis to compare the efficacy and safety of investigational drugs from phase III randomized controlled trials for the first-line treatment of EGFR-mutated NSCLC.
Results
Two studies were included in the analysis: FLAURA2 and MARIPOSA, evaluating the osimertinib-chemotherapy and amivantamab-lazertinib combinations, respectively. Overall survival (OS) data were immature at the time of the analysis. In progression free survival (PFS), there was a statistically significant difference favoring the FLAURA2 in the intention-to-treat (ITT) population [Hazard ratio (HR) 0.79], in patients with central nervous system (CNS) metastases (HR 0.63), without liver metastases (HR 0.73), and with EGFR L858R (HR 0.68). In intracranial PFS (icPFS), there was a statistically significant difference favoring the FLAURA2 (HR 0.52). We found no significant differences in efficacy in patients without CNS metastases, with liver metastases, and with exon 19 deletions. No new safety signals resulted from the safety analysis. In the FLAURA2, anemia, diarrhea, and neutropenia were more frequent; in the MARIPOSA, cutaneous rash and paronychia were more frequent instead.
Conclusions
Osimertinib-chemotherapy seems to be more effective in patients with EGFR L858R mutation and CNS metastases. However, neuroprotective effect could not be compared due to lack of data. The differences in the ITT are less marked and caution is needed in the interpretation of data due to the indirectness of methods. Other factors must be considered in the choice of the treatment, including the clinical characteristics of the patients, the safety profile of the combinations, and available facilities and personnel.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
A.J. Gelibter: Financial Interests, Personal, Invited Speaker: AstraZeneca, BMS, MSD, Roche, Takeda; Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, MSD, Roche, Takeda. G. Minuti: Financial Interests, Personal, Invited Speaker: AstraZeneca, Roche, BMS, Gilead, Novartis, Sanofi, Amgen, MSD, Johnson & Johnson, Daiichi Sankyo; Financial Interests, Personal, Advisory Board: AstraZeneca, Roche, BMS, Gilead, Novartis, Sanofi, Amgen, MSD, Johnson & Johnson, Daiichi Sankyo. L. Landi: Financial Interests, Personal, Invited Speaker: Pfizer, Novartis, AstraZeneca, AstraZeneca, Roche, BMS, MSD, Lilly, Amgen, Sanofi, AbbVie, Johnson & Johnson, Thermo Fisher; Financial Interests, Personal, Advisory Board: Pfizer, Novartis, Roche, BMS, MSD, Lilly, Amgen, Sanofi, AbbVie, Johnson & Johnson. F. Cappuzzo: Financial Interests, Personal, Advisory Board: Roche, AstraZeneca, BMS, Pfizer, Takeda, Lilly, Bayer, Amgen, Sanofi, Mirati, PharmaMar, Novocure, OSE, GALECTO and MSD; Financial Interests, Personal, Invited Speaker: Roche, AstraZeneca, BMS, Pfizer, Takeda, Lilly, Bayer, Amgen, Sanofi, PharmaMar, Mirati, Novocure, OSE, and MSD. All other authors have declared no conflicts of interest.