Osimertinib Is More Effective than Standard Therapy in EGFR^T790M Tumors

EGFR tyrosine kinase inhibitors (TKI) achieve high initial response rates in patients with EGFR-mutant advanced non–small cell lung cancer, but disease progression follows in the majority of patients, often due to the EGFR^T790M mutation that promotes resistance to first- and second-generation EGFR TKIs. Osimertinib is an oral, irreversible EGFR TKI that has demonstrated activity against EGFR^T790M and has shown promise in phase I and II trials for the treatment of patients with EGFR^T790M lung cancer. In an open-label phase III trial, Mok and colleagues compared the efficacy of osimertinib with platinum therapy plus pemetrexed as standard of care. A total of 419 patients with advanced EGFR^T790M non–small cell lung cancer who had progressed after first-line EGFR-TKI therapy were enrolled; 279 received osimertinib and 140 received platinum therapy plus pemetrexed. The primary endpoint was investigator-assessed progression-free survival, and secondary objectives included response rate, and safety and side-effect profiles. The median duration of progression-free survival was longer in osimertinib-treated patients, 10.1 months compared with 4.4 months for platinum–pemetrexed, and the objective response rate was 71% with osimertinib, but only 31% with platinum–pemetrexed. Osimertinib treatment also extended the duration of progression-free survival in the 144 patients with metastases to the central nervous system (CNS), 8.5 months in patients receiving osimertinib versus 4.2 months in patients receiving platinum–pemetrexed. Further, osimertinib was associated with fewer adverse events, with 23% of osimertinib-treated patients experiencing grade 3 or higher adverse events compared with 47% of platinum–pemetrexed-treated patients. Taken together, the results of this phase III trial demonstrate that osimertinib is more effective than platinum therapy plus pemetrexed in patients with EGFR^T790M lung cancer who have progressed on first-line EGFR TKIs, and indicate that osimertinib has activity even in patients with CNS metastases.

Mok TS, Wu YL, Ahn MJ, Garassino MC, Kim HR, Ramalingam SS, et al. Osimertinib or platinum-pemetrexed in EGFR T790M-positive lung cancer. N Engl J Med 2017;376:629–40.

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