The Food and Drug Administration has converted accelerated approval of osimertinib to full approval for the treatment of patients with metastatic epidermal growth factor receptor (EGFR) T790M mutation–positive non–small cell lung cancer (NSCLC), as detected by an FDA-approved test.
Also included in the indication, disease must have progressed on or after EGFR tyrosine kinase inhibitor (TKI) therapy, the FDA said in a statement .
The FDA granted accelerated approval of the drug for this indication in late 2015 based on an overall response rate (ORR) of 59% among 411 patients in two single-arm trials.
Full approval was based on an improvement in progression-free survival (PFS) in the phase III AURA3 study, which randomized 419 patients (2:1) to receive osimertinib (n = 279) 80 mg orally once daily or platinum-based doublet chemotherapy (n = 140). The hazard ratio for the investigator-assessed PFS was .30 (95% confidence interval: 0.23, 0.41; P less than .001).
The estimated median PFS was 10.1 months in the osimertinib arm and 4.4 months in the chemotherapy arm. Confirmed ORR was 65% (95% CI: 59%, 70%) and 29% (95% CI: 21%, 37%) in the osimertinib and chemotherapy arms, respectively (P less than .0001). Estimated median response durations were 11 months (95% CI: 8.6, 12.6) and 4.2 months (95% CI: 3.9, 5.9) in the osimertinib and chemotherapy arms, respectively, according to the FDA statement.
Overall survival data are immature, the FDA said.
All patients had metastatic EGFR T790M mutation–positive NSCLC, identified by the cobas EGFR mutation test performed in a central laboratory, and progressive disease following first-line EGFR TKI therapy. Patients in the chemotherapy arm received either pemetrexed, 500 mg/m2 with carboplatin AUC5, or pemetrexed, 500mg/m2 with cisplatin 75 mg/m2), on day 1 of every 21-day cycle for up to six cycles followed by pemetrexed maintenance therapy.
The most serious adverse reactions, evaluated in 833 patients receiving osimertinib, were interstitial lung disease/pneumonitis (3.5%), QTc interval prolongation (0.7%), cardiomyopathy (1.9%), and keratitis (0.7%). The most common adverse reactions were diarrhea, rash, dry skin, nail toxicity, and fatigue.
The recommended dose of osimertinib, to be marketed as Tagrisso by AstraZeneca, is 80 mg orally once daily, with or without food, until disease progression or unacceptable toxicity. The presence of an EGFR T790M mutation in a tumor specimen, or plasma specimen (if tumor tissue is unavailable), should be confirmed by an FDA-approved test prior to initiation of treatment.
Full prescribing information is available here .