FDA approves osimertinib for locally advanced, unresectable (stage III) non-small cell lung cancer following chemoradiation therapy

Regulatory approval: On Sept 25, 2024, the FDA approved osimertinib (Tagrisso) for adults with locally advanced, unresectable stage III NSCLC whose disease has not progressed during or after concurrent or sequential platinum-based chemoradiation and whose tumors harbor EGFR exon 19 deletions or exon 21 L858R mutations (FDA-approved test required). Approval was supported by LAURA (NCT03521154), where osimertinib significantly improved PFS vs placebo (HR 0.16; median 39.1 vs 5.6 months). OS data were immature.

FDA approval (Sept 25, 2024)

The US Food and Drug Administration (FDA) approved osimertinib (Tagrisso; AstraZeneca Pharmaceuticals) for adult patients with locally advanced, unresectable (stage III) non-small cell lung cancer (NSCLC) whose disease has not progressed during or following concurrent or sequential platinum-based chemoradiation therapy, and whose tumors have EGFR exon 19 deletions or exon 21 L858R mutations as detected by an FDA-approved test.

Supporting evidence: LAURA (NCT03521154)

Approval was supported by LAURA, a double-blind, randomized, placebo-controlled trial in 216 adults with unresectable stage III EGFR-mutated NSCLC without progression during or after definitive platinum-based chemoradiation within 42 days prior to randomization. Patients were randomized 2:1 to osimertinib 80 mg orally once daily or placebo until progression or unacceptable toxicity.

  • Primary endpoint: PFS by blinded independent central review
  • PFS: HR 0.16 (95% CI 0.10–0.24; p<0.001); median 39.1 months (95% CI 31.5–NE) vs 5.6 months (95% CI 3.7–7.4)
  • OS: immature at current analysis (36% of pre-specified deaths); no trend toward detriment reported

Safety and dosing

Common adverse reactions/lab abnormalities (≥20%) included lymphopenia, leukopenia, ILD/pneumonitis, thrombocytopenia, neutropenia, rash, diarrhea, nail toxicity, musculoskeletal pain, cough, and COVID-19 infection. Recommended dose: 80 mg once daily, with or without food, until progression or unacceptable toxicity.

Regulatory notes

Review used Project Orbis; partner agency reviews (TGA, Health Canada, Swissmedic) were ongoing. The application received priority review and breakthrough designation.

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