What’s up, dac?

Top Line: So what's up with dacomitinib?
The Study: This second-generation EGFR-TKI first made headlines last year with reporting of the primary endpoint of the phase 3 Asian ARCHER 1050 trial, which demonstrated a significant progression-free survival advantage with dacomitinib versus the standard first-generation gefitinib. This month finally brings us the news that, while a secondary endpoint, is of primary concern. That’s right, the overall survival analysis. As a refresher, the ARCHER 1050 trial randomized 452 patients with untreated EGFR-aberrant Stage IIIB-IV NSCLC to daily dacomitinib 45 mg or gefitinib 250 mg. At time of pre-specified analysis, median overall survival was longer among those receiving upfront dacomitib (34 months) than gefitinib (27 months). One reason this is big news is that it’s the first EGFR-TKI to prove an actual overall survival advantage when pitted head to head against one of its own. Another interesting observation is that, while the vast majority of patients receiving salvage systemic therapy moved on to chemo, the few who went straight to a third-generation EGFR-TKI (aka osimertinib) had the highest numeric median survival of all. Finally, brain mets were an important exclusion criterion to note, though this Pfizer-sponsored pub is quick to highlight that site of first failure occurred intracranially in only a single patient randomized to upfront dacomitinib.
Bottom Line: Dacomitinib improves overall survival compared with gefitinib among (mostly) Asian patients with EGFR-aberrant NSCLC, but verdict is still out on how it stacks up next to its progeny osimertinib. | Mok, J Clin Oncol 2018


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