In the phase I study PROFILE 1001, crizotinib showed marked antitumor activity in advanced ROS1-rearranged NSCLC (Shaw, N Engl J Med 2014). We present updated data for 53 patients (pts) with ROS1-rearranged NSCLC from this ongoing study (NCT00585195).
ROS1 status was determined by break-apart FISH test or RT-PCR test. All pts received crizotinib at a starting dose of 250 mg orally twice daily.
Fifty-three pts enrolled and were treated with crizotinib for a median treatment duration of 23.2 months. All were included in the efficacy and safety analyses. At data cutoff (November 30, 2014), treatment was ongoing in 25 pts (47%). The median age of pts was 55 years, 57% were female, and 57% and 40% were white and Asian, respectively; all were never or former smokers. The objective response rate (ORR) was 70% (95% CI: 56, 82), which included five complete responses and 32 partial responses; 11 pts had stable disease. By independent radiology review (n = 50), ORR was 66% (95% CI: 51, 79). Responses were durable (median duration of response not reached [NR]; 95% CI: 15.2, NR). ORR was consistent across baseline and disease characteristics, and appeared independent of the percentage of ROS1-rearranged cells. Median progression-free survival was 19.3 months (95% CI: 14.8, NR). At a median follow-up of 25.4 months, median overall survival was NR; the probabilities of survival at 6 and 12 months were 91% (95% CI: 79, 96) and 79% (95% CI: 65, 88), respectively. The safety profile was similar to that of crizotinib in pts with ALK-positive NSCLC. The most common treatment-related adverse events (TRAEs) were vision disorder (85%), nausea (49%), edema (45%), diarrhea (42%), and vomiting (38%), mainly grade 1 or 2 in severity. The most common grade 3 TRAEs were hypophosphatemia (13%), neutropenia (9%), and elevated transaminases (4%), and there were no grade 4 TRAEs. Of 16 deaths on study, none were attributed to crizotinib.
These updated data confirm the clinically meaningful benefit and safety of crizotinib in pts with advanced ROS1-rearranged NSCLC.
Clinical trial identification
Legal entity responsible for the study
Y-J. Bang: Research funding from Pfizer to their institution. D.R. Camidge: Honararia from Pfizer. M. Winter, T. Usari, S.C. Wang, K. Wilner: Pfizer employee. All other authors have declared no conflicts of interest.