A New First-Line Standard for EGFR-Mutated NSCLC?

Among patients with non–small-cell lung cancer (NSCLC) and sensitizing mutations in the epidermal growth factor receptor (EGFR) gene, the primacy of first-line osimertinib monotherapy has been challenged by two combination regimens. The MARIPOSA trial showed progression-free survival (PFS) and overall-survival (OS) benefits of amivantamab–lazertinib over osimertinib alone. The phase 3, open-label FLAURA2 trial previously showed a PFS benefit of platinum-pemetrexed chemotherapy with osimertinib over osimertinib alone; the current update reports OS results, a key secondary end point. Investigators randomized 557 patients with locally advanced or metastatic NSCLC and sensitizing EGFR mutations to first-line treatment with osimertinib plus platinum-pemetrexed chemotherapy (four induction cycles of platinum doublet, followed by maintenance with a median 11 cycles of pemetrexed, with daily osimertinib throughout) or to osimertinib alone.

Key results were as follows:

• Median OS was significantly longer with combination therapy than with osimertinib alone: 48 months versus 38 months.
• OS benefit occurred among patients with and without brain metastases and with either L858R or exon 19 deletion.
• The median duration of osimertinib exposure was 31 months in the combination-therapy group and 21 months in the monotherapy group.
• The combination-therapy group had a higher rate of grade 3 or higher adverse events (70% vs. 34%), most commonly anemia, neutropenia, and decreased platelet count. Onset of adverse events with combination therapy was most frequent during induction and decreased during maintenance.