FDA approves osimertinib with chemotherapy for EGFR-mutated non-small cell lung cancer

Regulatory approval: On Feb 16, 2024, the FDA approved osimertinib (Tagrisso) in combination with platinum-based chemotherapy for patients with locally advanced or metastatic NSCLC whose tumors harbor EGFR exon 19 deletions or exon 21 L858R mutations (per an FDA-approved test). Approval was supported by the phase 3 FLAURA 2 trial, where osimertinib plus chemotherapy significantly improved investigator-assessed PFS versus osimertinib alone (HR 0.62; median 25.5 vs 16.7 months). OS data were immature.

FDA approval: osimertinib plus platinum chemotherapy in EGFR-mutated la/mNSCLC (Feb 16, 2024)

Type: Regulatory approval (FDA)

On February 16, 2024, the FDA approved osimertinib (Tagrisso; AstraZeneca) with platinum-based chemotherapy for patients with locally advanced or metastatic non-small cell lung cancer (la/mNSCLC) whose tumors have EGFR exon 19 deletions or exon 21 L858R mutations, as detected by an FDA-approved test.

Supporting evidence (FLAURA 2; NCT04035486)

FLAURA 2 was an open-label, randomized trial in 557 patients with EGFR exon 19 deletion– or exon 21 L858R–positive la/mNSCLC and no prior systemic therapy for advanced disease, randomized 1:1 to osimertinib + platinum-based chemotherapy vs osimertinib monotherapy.

  • Primary endpoint: investigator-assessed PFS; OS was a key secondary endpoint.
  • PFS: statistically significant improvement with combination therapy (HR 0.62, 95% CI 0.49–0.79; p<0.0001). Median PFS was 25.5 months (95% CI 24.7–NE) vs 16.7 months (95% CI 14.1–21.3).
  • OS: immature at the time of analysis (45% of pre-specified deaths); no trend toward detriment was observed.

Safety and dosing highlights

Common adverse reactions (≥20%) with the combination included leukopenia, thrombocytopenia, neutropenia, lymphopenia, rash, diarrhea, stomatitis, nail toxicity, dry skin, and increased blood creatinine. Recommended osimertinib dose: 80 mg orally once daily until progression or unacceptable toxicity.

The review was conducted under Project Orbis; partner-agency reviews were reported as ongoing.

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