Chemotherapy rechallenge after osimertinib-chemotherapy in FLAURA-2

Previously, the pivotal FLAURA2 study demonstrated that adding platinum–pemetrexed chemotherapy to first line osimertinib significantly improved the progression-free (PFS) and overall survival (OS) of patients with EGFR-mutant, advanced non-small cell lung cancer (NSCLC). At ELCC 2026, Dr Carles Escriu, medical oncologist at the Clatterbridge Cancer Centre in Liverpool, presented the results of a post-hoc analysis of this trial zooming in on treatment patterns and outcomes following disease progression, with a particular emphasis on the feasibility and effectiveness of chemotherapy rechallenge. In this video, Dr Escriu discusses the key takeaways from this analysis with Prof Dr Mariana Brandão, medical oncologist at the Jules Bordet Institute in Brussels.

At three years post-randomization, 46% of patients in the combination arm had discontinued therapy due to disease progression, compared to 67% in the osimertinib monotherapy arm. Among patients eligible for subsequent therapy, about 75% in both groups received further chemotherapy. However, notable differences were seen in the specific chemotherapy that was used. In fact, 44% of patients previously exposed to platinum-based chemotherapy underwent platinum rechallenge, whereas approximately 70% of patients initially treated with osimertinib alone received platinum-based regimens upon progression.

Among patients who initially received osimertinib-chemotherapy and received post-progression therapy, a better OS was observed with subsequent platinum-based chemotherapy compared to non-platinum-based chemotherapy or other treatment options (3-year OS rate: 77% vs. 65% and 27%, respectively). In the control arm, OS data after subsequent platinum-based chemotherapy were more modest, with a 3-year OS rate of only 42%.  The median duration of the chemotherapy-free interval in the osimertinib plus platinum–pemetrexed was reported at 10.4 months but varied widely from 0.5 to 49.9 months. This wide range suggests that patient selection and disease biology likely had an important influence on treatment decisions and outcomes. In fact, patients with longer intervals between treatments likely had more indolent disease and better performance status, making them more suitable candidates for rechallenge.

Overall, these findings provide reassurance that the use of first-line combination therapy does not diminish the efficacy of subsequent chemotherapy. On the contrary, chemotherapy rechallenge appears to remain a clinically meaningful and effective strategy in this setting. How to position this approach relative to emerging alternatives, such as the combination of amivantamab with chemotherapy, remains an open question and should be the focus of ongoing clinical investigation and future debate.