Profile 1014 trial shows overall survivaL data for Xalkori (crizotinib) in previously untreated patients with ALK-positive advanced non-small cell lung cancer.- Pfizer

Pfizer Inc. announced final overall survival (OS) data from the PROFILE 1014 trial examining Xalkori (crizotinib) in previously untreated patients with ALK-positive advanced non-small cell lung cancer(NSCLC). After a median follow-up of 46 months, the median OS for patients randomized to Xalkori was not reached (95% CI: 45.8 months, not reached) and was 47.5 months for patients randomized to chemotherapy (95% CI: 32.2 months, not reached). Results indicated a numerical improvement in OS for patients treated with first-line Xalkori compared with chemotherapy, though this difference did not quite achieve statistical significance (HR=0.760 [95% CI: 0.548, 1.053]; p=0.0978).

These data [Abstract #LBA50] were presented at the 2017 European Society for Medical Oncology (ESMO) Congress in Madrid, Spain. The majority (84%) of patients initially randomized to chemotherapy received Xalkori after they progressed and this likely affected the overall survival results. A pre-specified, exploratory statistical analysis, adjusting for the effects of crossover, determined that median OS would have been longer for patients randomized to Xalkori than for patients randomized to chemotherapy, if patients had not been allowed to cross over [HR: 0.346 (95% CI: 0.081, 0.718)].

Comment:This is the first set of prospective data from a randomized Phase III study to report long-term survival outcomes for patients with ALK-positive non-small cell lung cancer. The longest survival outcomes were in patients who received two or more tyrosine kinase inhibitors, which provides insight into optimal treatment sequencing.

Overall survival was a secondary endpoint of PROFILE 1014 and the threshold for statistical significance was p less than 0.0247. PROFILE 1014 was a global, randomized, open-label, two-arm Phase III study that evaluated the efficacy and safety of Xalkori in patients with previously untreated ALK-positive advanced NSCLC. Progression-free survival (PFS) was the primary endpoint, and these results were previously published in The New England Journal of Medicine (NEJM). There was a statistically significant improvement in PFS in the patients treated with Xalkori than with chemotherapy (p<0.001)