First-line treatment in EGFR-mutated non-small cell lung cancer. Brief report of an individual patient data comparison of phase 3 clinical trials

Introduction: Clinical trials evaluated the efficacy and safety of novel first-line treatment strategies for advanced epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC), relative to osimertinib monotherapy. Methods: After review of the literature, we performed an individual patient data comparison of efficacy and safety of investigational regimens from phase 3 randomized controlled trials in untreated EGFR-mutated NSCLC. Results: Two studies were included in the analysis: FLAURA2 and MARIPOSA, evaluating the osimertinib-chemotherapy and amivantamab-lazertinib combinations, respectively. In progression free survival (PFS), there was a statistically significant difference favoring the FLAURA2 in the intent-to-treat (ITT) population [Hazard ratio (HR) 0.79], not confirmed in the overall survival (OS) analysis where we did not find any significant difference. FLAURA2 PFS was longer 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 differences in PFS in patients without CNS metastases, and with exon 19 deletions. No new safety signals resulted from the safety analysis. In FLAURA2, anemia, diarrhea, and neutropenia were more frequent, while in MARIPOSA rash and paronychia. Conclusion: In the ITT population, we found no differences in OS between amivantamab-lazertinib and osimertinib-chemotherapy, despite a slightly higher PFS of the latter. Osimertinib-chemotherapy could be more effective in patients with CNS metastases, without liver metastases, and EGFR L858R mutation, however we could not compare OS in these subgroups. Due to the indirect nature of the comparison and the limitation of the methods our results are not definitive, but rather hypothesis-generating. Other factors must be considered in the choice of the treatment, including patient's characteristics, the safety profile of the combinations, and center's facilities and expertise.