PFS Improved With Osimertinib in Certain NSCLC

First-line osimertinib combined with chemotherapy significantly lengthened investigator-assessed progression-free survival (PFS) compared with osimertinib alone in patients with advanced nonsquamous non–small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR)-sensitizing and concurrent TP53 mutations, according to a randomized phase 3 trial (TOP) published online in JAMA.

The open-label study enrolled 294 treatment-naive patients with stage IV or recurrent disease at 17 sites in China from March 25, 2021, through July 11, 2024. Participants were randomized 1:1 to osimertinib plus pemetrexed and carboplatin every 3 weeks for 4 cycles, followed by maintenance osimertinib plus pemetrexed (n=146), or osimertinib monotherapy (n=148). Median age was 57 years, and 54.1% of participants were female.

At the November 11, 2025, data cutoff, median follow-up was 25.1 months in the combination group and 26.1 months in the monotherapy group. Median PFS was 34.0 months with combination therapy and 15.6 months with osimertinib alone, a difference of 18.4 months. The benefit was consistent across prespecified subgroups, including patients with brain metastases and L858R mutations.

Overall survival data were immature at 30.6% maturity, although investigators observed a trend favoring combination therapy. Grade 3 or higher treatment-related adverse events occurred more often with the combination, with no new safety signal identified.

The investigators concluded that the findings provide a clinical rationale for individualized combination strategies in patients with EGFR-mutated NSCLC and concurrent TP53 mutations.

Source: Zhou T, Zhou H, Gao F, et al. Osimertinib with or without chemotherapy in advanced non–small cell lung cancer with EGFR and concurrent TP53 mutations: a randomized clinical trial. JAMA. Published online August 10, 2026. doi:10.1001/jama.2026.10599