The FDA has approved osimertinib for adult patients with stage III NSCLC whose tumors have specific EGFR mutations, following chemoradiation therapy.

RT’s Three Key Takeaways:

  1. FDA Approval: Osimertinib has been approved for adult patients with unresectable stage III non-small cell lung cancer (NSCLC) who have specific EGFR mutations and whose disease has not progressed following chemoradiation therapy.
  2. Clinical Trial Results: In the LAURA trial, osimertinib significantly improved progression-free survival, with a median of 39.1 months compared to 5.6 months for placebo, demonstrating a strong efficacy in delaying disease progression.
  3. Safety Profile: The most common adverse reactions to osimertinib include lymphopenia, leukopenia, interstitial lung disease, rash, diarrhea, and musculoskeletal pain, but overall survival data are still being evaluated.

The US Food and Drug Administration has approved osimertinib (Tagrisso, AstraZeneca) 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.

Efficacy was evaluated in LAURA, a double blind, randomized, placebo-controlled trial in 216 adult patients with locally advanced, unresectable stage III NSCLC with EGFR exon 19 deletions or exon 21 L858R mutations who had not progressed during or following definitive platinum-based chemoradiation within 42 days prior to study randomization. Patients were randomized (2:1) to receive either osimertinib 80 mg orally once daily or placebo until disease progression or unacceptable toxicity.

[RELATED: FDA Approves Osimertinib Plus Chemotherapy for EGFR-mutated NSCLC]

The major efficacy outcome measure was progression-free survival as assessed by blinded independent central review. Additional efficacy outcome measures included overall survival. Osimertinib demonstrated a statistically significant improvement in progression free survival compared to placebo with a hazard ratio of 0.16 (95% CI: 0.10, 0.24; p-value <0.001). 

The median progression free survival was 39.1 months (95% CI: 31.5, not estimable [NE]) in the osimertinib arm and 5.6 months (95% CI: 3.7, 7.4) in the placebo arm.

While overall survival results were immature at the current analysis, with 36% of pre-specified deaths for the final analysis reported, no trend towards a detriment was observed.

The most common adverse reactions, including laboratory abnormalities (≥20%), were lymphopenia, leukopenia, interstitial lung disease/pneumonitis, thrombocytopenia, neutropenia, rash, diarrhea, nail toxicity, musculoskeletal pain, cough, and COVID-19 infection.

The recommended osimertinib dose is 80 mg once daily, with or without food, until disease progression or unacceptable toxicity.

This review was conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence. Project Orbis provides a framework for concurrent submission and review of oncology drugs among international partners. For this review, FDA collaborated with the Australian Therapeutic Goods Administration, Health Canada, and Switzerland’s Swissmedic. The application reviews are ongoing at the other regulatory agencies.

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