Long live ALK-targeted therapies.

Top Line: With improving ALK-targeted therapies for non-small cell lung cancer (NSCLC), can we forget plain-ole cemo altogether? 
The Study: We’ve known since the initial 2014 landmark reporting of the PROFILE 1014 trial, when compared to pemetrexed/platinum chemo, upfront crizotinib improves median progression-free survival (PFS) from 7 → 11 months for ALK-rearranged NSCLC. While that was technically the primary endpoint, what we’re all really interested in is actual survival. As a reminder, PROFILE 1014 enrolled 343 patients with locally advanced (n=5) or metastatic (n=336)—ok so really just metastatic—previously untreated disease and randomized them 1:1 to chemo:crizotinib. Importantly, crossover was allowed, and 144 (84%) of those assigned to chemo went on to get crizotinib. Now the overall survival results are finally here. Why now? Because every single patient has discontinued the study...after all, the protocol was written to last an optimistic 36 months. Why not sooner? Because median overall survival was an unprecedented 4 years or more: 48 months with upfront chemo (plus a whole lotta subsequent crizotinib) and still not reached for upfront crizotinib. Looking at the forest plot of subgroup analyses, the only group who visually fared worse with upfront crizotinib were those with brain mets (we see you, brigatinib). As the authors rightly conclude, this sets a new benchmark for overall survival times.
Bottom Line: Crizotinib achieves unprecedented survival for patients with ALK-rearranged NSCLC.  | Solomon, J Clin Oncol 2018


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