Osimertinib latest news: European Commission approves osimertinib in combination with chemotherapy for the treatment of advanced EGFR+ NSCLC

The European Union has approved the use of osimertinib (Tagrisso) in combination with pemetrexed and platinum-based chemotherapy for adult patients with advanced non-small cell lung cancer (NSCLC) carrying EGFR exon 19 deletions or exon 21 L858R mutations.

The regulatory decision is based on results from the FLAURA2 Phase 3 trial (NCT04035486), which also supported the European Medicines Agency's Committee for Medicinal Products for Human Use's positive opinion on the use of the combination in this indication. The results of the FLAURA2 study published in the New England Journal of Medicine showed that the median progression-free survival (PFS) of osimertinib combined with chemotherapy was 25.5 months (95% CI, 24.7-not countable). Calculated [NC]), the median survival for osimertinib monotherapy was 16.7 months, 95% CI, 14.1-21.3 (HR, 0.62; 95% CI, 0.49-0.79; P<.0001). Median PFS by blinded independent central review (BICR) was 29.4 months (95% CI, 25.1 to NC, 0.62; 95% confidence interval, 0.48 to 0.80; nominal P = .0002).

Additionally, a prespecified exploratory analysis of FLAURA2 patients with brain metastases at baseline showed that osimertinib plus chemotherapy reduced the risk of BICR-assessed central nervous system (CNS) disease progression or death by 42% compared with osimertinib monotherapy (HR, 0.58; 95% CI, 0.33-1.01).

Although overall survival (OS) data were premature at the time of the second interim analysis, researchers observed a trend favoring osimertinib plus chemotherapy versus osimertinib monotherapy (HR, 0.75; 95% CI, 0.57-0.97). The 24-month OS rates of the combination therapy group and the monotherapy group were 79% (95% CI, 73%-83%) and 73% (95% CI: 67%-78%), respectively. FLAURA2 will continue to assess OS as a key secondary endpoint.

This approval marks a significant advance for patients with EGFR-mutated cancers in Europe, providing a new first-line treatment option for osimertinib in combination with chemotherapy. FLAURA2 results build on the established efficacy of osimertinibmonotherapy and show meaningful[8.8] month PFS improvement and provides physicians with the option to tailor treatment to patients' specific needs.

This approval strengthens osimertinib as a backbone therapy for EGFR-mutant cancers, either as monotherapy or in combination with chemotherapy. This is particularly important for patients with more severe disease, including those whose cancer has spread to the brain and those with the L858R mutation.

The safety profile observed duringFLAURA2 of osimertinibin combination with chemotherapy was consistent with the established safety profile of the individual agents. The incidence of adverse reactions was higher in the combination group compared with the monotherapy group because chemotherapy-related adverse effects are well characterized. Eleven percent of patients in the combination therapy group discontinued osimertinib due to adverse events, compared with 6% of patients in the monotherapy group.

In February 2024, the U.S. Food and Drug Administration approved osimertinib in combination with chemotherapy for the first-line treatment of patients with locally advanced or metastatic NSCLC carrying EGFR exon 19 deletions or exon 21 L858R mutations.