On February 16, the U.S. Food and Drug Administration (FDA) approved osimertinib (Tagrisso) with platinum-based chemotherapy for patients with locally advanced or metastatic non–small cell lung cancer (NSCLC) whose tumors have EGFR exon 19 deletions or exon 21 L858R mutations, as detected by an FDA-approved test.
FLAURA2
Efficacy was evaluated in FLAURA2 (ClinicalTrials.gov identifier NCT04035486), an open-label, randomized trial of 557 patients with EGFR exon 19 deletion or exon 21 L858R mutation–positive locally advanced or metastatic NSCLC and no prior systemic therapy for advanced disease. Patients were randomly assigned 1:1 to receive either osimertinib with platinum-based chemotherapy or osimertinib monotherapy.
The major efficacy outcome measure was investigator-assessed progression-free survival, with overall survival as a key secondary outcome measure. Osimertinib plus platinum-based chemotherapy demonstrated a statistically significant improvement in progression-free survival compared to osimertinib monotherapy, with a hazard ratio of 0.62 (95% confidence interval [CI] = 0.49–0.79, two-sided P < .0001). Median progression-free survival was 25.5 months (95% CI = 24.7 months to not estimable) and 16.7 months (95% CI = 14.1–21.3 months) in the respective arms.
While overall survival results were immature at the time of the current analysis, with 45% of prespecified deaths for the final analysis reported, no trend toward a detriment was observed.
The most common adverse reactions—occurring in ≥ 20% of patients receiving osimertinib plus platinum-based chemotherapy—were leukopenia, thrombocytopenia, neutropenia, lymphopenia, rash, diarrhea, stomatitis, nail toxicity, dry skin, and increased blood creatinine.
Additional Dosing and Regulatory Information
The recommended osimertinib dose is 80 mg orally once daily with or without food until disease progression or unacceptable toxicity. Refer to the prescribing information for pemetrexed and cisplatin or carboplatin for their respective dosing information.
This review was conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence which provides a framework for the 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.
This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment. This application was granted Priority Review, Fast Track designation, Regenerative Medicine Advanced Therapy designation, and Orphan Drug designation.
