On September 25, the U.S. Food and Drug Administration approved osimertinib (Tagrisso) for adults with locally advanced, unresectable (stage III) non–small cell lung cancer (NSCLC) whose disease has not progressed during or after concurrent or sequential platinum-based chemoradiation therapy. These patients also must have tumors with EGFR exon 19 deletions or exon 21 L858R mutations, as detected by an FDA-approved test.
Efficacy and Safety
Efficacy was evaluated in the LAURA trial (ClinicalTrials.gov identifier NCT03521154), a double blind, randomized, placebo-controlled trial. It included 216 adults with locally advanced, unresectable stage III NSCLC whose tumors have EGFR exon 19 deletions or exon 21 L858R mutations and had not experienced disease progression during or after definitive platinum-based chemoradiation within 42 days prior to study randomization. Patients were randomly assigned (2:1) to receive either osimertinib at 80 mg orally once daily or placebo until disease progression or unacceptable toxicity.
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 vs placebo, with a hazard ratio of 0.16 (95% confidence interval [CI] = 0.10–0.24; P < .001). The median progression-free survival was 39.1 months (95% CI = 31.5 months to not estimable) in the osimertinib arm and 5.6 months (95% CI = 3.7–7.4 months) in the placebo arm.
Although overall survival results were immature at the current analysis, with 36% of prespecified deaths for the final analysis reported, no trend toward 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. Full prescribing information for osimertinib, see Drugs@FDA.
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, the FDA collaborated with the Australian Therapeutic Goods Administration, Health Canada, and Switzerland’s Swissmedic. The application reviews are ongoing at the other regulatory agencies.
