Pfizer 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)].

“PROFILE 1014 has provided important new data for patients with non-small cell lung cancer," said Professor Tony Mok, Chair of Department of Clinical Oncology, The Chinese University of Hong Kong. "This is the first set of prospective data from a randomized Phase 3 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=0.0247.1 PROFILE 1014 was a global, randomized, open-label, two-arm Phase 3 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). A total of 343 patients were randomized into the trial, with approximately half of the patients in the Xalkori arm and the other half of the patients in the platinum doublet chemotherapy arm.

“Xalkori was the first biomarker-driven therapy for ALK-positive NSCLC and as such, dramatically changed the treatment paradigm for these patients. It remains the only ALK inhibitor with mature survival data from a randomized Phase 3 trial. We are extremely proud of the impact Xalkori continues to make on patients’ lives,” said Mace Rothenberg, MD, chief development officer, Oncology, Pfizer Global Product Development.

The most commonly reported adverse events with Xalkori were vision disorder (71%), diarrhea (61%), nausea (56%) and edema (49%), and with chemotherapy, nausea (59%), fatigue (38%), vomiting (36%) and decreased appetite (34%). Most adverse events in both treatment groups were grade 1 or 2 in severity. Grade 3 or 4 elevations of aminotransferase levels occurred in 14% of patients in the Xalkori group and 2% of patients in the chemotherapy group, and these elevations were managed primarily with dose interruptions or dose reductions. Grade 3 or 4 neutropenia occurred in 11% and 15% of patients in the Xalkori and chemotherapy groups, respectively, with no cases of febrile neutropenia reported with Xalkori and two cases with chemotherapy.