Osimertinib Granted FDA Approval for Metastatic Non-Small Cell Lung Cancer

The FDA granted regular approval to osimertinib (Tagrisso) for the treatment of metastatic epidermal growth factor receptor (EGFR) T790M mutation-positive non-small cell lung cancer (NSCLC) that has progressed on or after EGFR tyrosine kinase inhibitor (TKI) therapy.

The approval was based on data from the randomized, multicenter, open-label, active-controlled, AURA3 (NCT012151981) trial, which included 419 patients with metastatic EGFR T790M mutation-positive NSCLC who had progressive disease following first-line EGFR TKI therapy, according to a press release.

For the AURA3 trial, patients were randomized 2:1 to receive either 80 mg of osimertinib orally once-daily or platinum-based doublet chemotherapy. Participants in the chemotherapy arm received either 500 mg/m2 of pemetrexed with carboplatin AUC5, or 500 mg/m2 of pemetrexed with 75 mg/m2 of cisplatin. Dosages were administered on day 1 of every 21-day cycle for up to 6 cycles, followed by pemetrexed maintenance therapy.

Patients in the chemotherapy arm with radiological progression were offered osimertinib at progression, according to both investigators and blinded independent central review.

The results of the study showed improvement in progression-free survival (PFS), with a HR of 0.30. The estimated median PFS was 10.1 months in the osimertinib arm and 4.4 months in the chemotherapy arm.

The confirmed overall response rate (ORR) was 65% in the osimertinib arm and 29% in the chemotherapy arm. Estimated median response durations were 11 moths and 4.2 months, respectively.

The confirmed central nervous system (CNS) ORR in patients with measurable CNS lesions on baseline brain scans were 57% in the osimertinib arm and 25% in the chemotherapy arm. The median CNS response duration was unmet in the osimertinib arm and was 5.7 months in the chemotherapy arm. The overall survival data are immature, according to the release.

Reports of serious adverse events (AEs) in the osimertinib arm were interstitial lung disease/pneumonitis, QTc interval prolongation, cardiomyopathy, and keratitis. The most common AEs, which occurred in at least 20% of patients, were diarrhea, rash, dry skin, nail toxicity, and fatigue.

Osimertinib received accelerated approval for this indication in November 2015, based on an ORR of 59% among 411 patients in 2 single-arm clinical trials.