The full approval comes in less than 2 years of the drug's accelerated approval by the FDA.
A press announcement from AstraZeneca has confirmed the full approval of once-daily osimertinib (Tagrisso) for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) with a T790M mutation in the epidermal growth factor receptor (EGFR), confirmed using an FDA-approved diagnostic test.
The company submitted data from the phase 3 AURA3 trial,1 which used progression-free survival (PFS) as a marker to compare the effect of osimertinib with platinum-based doublet chemotherapy in patients with metastatic EGFR T790M mutation—positive NSCLC. Osimertinib (median PFS, 10.1 months) extended PFS by 5.7 months over chemotherapy (median PFS, 4.4 months), per the trial results (HR, 0.30; 70% risk reduction; 95% CI, 0.23-0.41; P <.001). The objective response rate was significantly better with osimertinib (71%; 95% CI, 65-76) than with platinum therapy plus pemetrexed (31%; 95% CI, 24-40; odds ratio, 5.39; 95% CI, 3.47-8.48; P <.001).
Among patients with advanced disease who had metastases to the nervous system, PFS was longer among those who received osimertinib (8.5 months vs 4.2 months; HR, 0.32; 95% CI, 0.21-0.49).
“The FDA’s full approval reinforces the potential of Tagrisso to become the standard of care for patients with metastatic EGFR T790M mutation-positive non-small cell lung cancer whose disease has progressed on or after first-generation EGFR-[tyrosine kinase inhibitor] therapy,” said Sean Bohen, executive vice president, Global Medicines Development and CMO at AstraZeneca.
More than 20% of osimertinib-treated patients experienced adverse events (AEs), with a majority (41%) experiencing diarrhea. Other AEs included rash (34%), dry skin (23%), nail toxicity (22%), and fatigue (22%). Serious AEs were reported in 18% of patients on osimertinib, compared with 26% of patients on chemotherapy.
Osimertinib received accelerated approval in late 2015, indicative of the drug’s importance in filling an unmet need for this specific group of patients. The FDA requires companies to continue phase 4 confirmatory trials to corroborate the anticipated clinical benefit, which resulted in the traditional approval that osimertinib has now received.
The drug doesn’t come cheap—a 3-month supply of the drug is estimated to cost about $13,000. In the United Kingdom, the National Institutes for Health and Care Excellence has rejected the drug in its preliminary recommendation, but then backtracked and put forth a recommendation for osimertinib to be financed via the Cancer Drugs Fund.
1. Mok TS, Wu Y-L, Ahn M-J, et al. Osimertinib or platinum—pemetrexed in EGFR T790M–positive lung cancer. N Engl J Med. 2017;376(7):629-640. doi: 10.1056/NEJMoa1612674.