FDA grants regular approval to Tagrisso for certain patients with NSCLC
The FDA granted regular approval to osimertinib for the treatment of certain patients with metastatic non–small cell lung cancer.
The approval allows osimertinib (Tagrisso, AstraZeneca) to be used for patients whose tumors harbor epidermal growth factor receptor T790M mutations detected by an FDA–test, and whose disease progressed on or after EGFR tyrosine kinase inhibitor therapy.
The FDA had granted accelerated approval to osimertinib for this indication in November 2015 based on results of two single-arm clinical trials, which showed the agent induced an overall response rate of 59%.
The agency based the regular approval on results of the randomized AURA3 trial, which included 419 patients with metastatic EGFR T790M mutation–positive NSCLC as identified by the cobas EGFR mutation test (Roche Molecular Systems). All patients had progressed after first-line therapy with an EGFR tyrosine kinase inhibitor.
Researchers randomly assigned 279 patients to osimertinib 80 mg orally once daily. The other 140 patients received platinum-based doublet chemotherapy. Those assigned chemotherapy received either pemetrexed 500 mg/m2 with carboplatin area under the curve 5, 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.
Patients assigned chemotherapy who experienced radiological progression according to both investigator and blinded independent central review could cross over to osimertinib.
Results showed osimertinib significantly extended PFS (median, 10.1 months vs. 4.4 months; HR = 0.3; 95% CI, 0.23-0.41).
Researchers also reported a higher overall response rate (65% vs. 29%; P < .0001) and longer median duration of response (11 months vs. 4.2 months) among osimertinib-treated patients.
Among patients whose baseline brain scans showed measurable central nervous system lesions, osimertinib appeared associated with a higher ORR (57% vs. 25%) and longer median CNS response duration (not reached vs. 5.7 months).
The most serious adverse events reported in osimertinib-treated patients include interstitial lung disease/pneumonitis (3.5%), cardiomyopathy (1.9%), QT interval prolongation (0.7%) and keratitis (0.7%). Adverse reactions that have occurred in at least 20% of patients included diarrhea, rash, nail toxicity, dry skin and fatigue.