Slow simer.

Top Line: Two years ago we learned that the third-generation EGFR-TKI osimertinib achieved unprecedented progression-free survival times as upfront therapy for EGFR-mutated non-small cell lung cancer (NSCLC).

The Study: We’re talking about the landmark FLAURA trial that randomized over 550 with locally-advanced / metastatic (read: 95% metastatic) EGFR-mutant NSCLC to upfront [1] osimertinib orally once daily versus [2] physician’s choice of the older gefitinib or erlotinib orally once daily. The primary endpoint—primary because it could place osimertinib on insurance coverage lists two years sooner—of progression-free survival was drastically improved from a median of 10 → 19 months (HR 0.46) with osimertinib. Now we have reporting of the secondary endpoint that’s primary in our hearts. In tow, median overall survival was significantly improved from a 32 → 39 months (HR 0.8). Importantly, patients in arm [2] with a T790M-mutation after progression were eligible to crossover to osimertinib, and 31% did so, likely diminishing the gap in overall survival. Plus the rates of toxicity between arms was virtually identical. Perhaps most celebrated should be the long wait time for survival events across the board.

TBL: Osimertinib, just like dacomitinib, given first-line for advanced EGFR-mutated NSCLC ineligible for definitive surgery or radiation has proven to confer superior overall survival times when compared to older-generation EGFR-TKIs. | Ramalingam, N Engl J Med 2020