Crizotinib in ROS1-rearranged advanced non-small-cell lung cancer (NSCLC): updated results, including overall survival, from PROFILE 1001

Abstract

Background: In the ongoing phase I PROFILE 1001 study, crizotinib showed antitumor activity in patients with ROS1-rearranged advanced non-small-cell lung cancer (NSCLC). Here, we present updated antitumor activity, overall survival (OS) and safety data (additional 46.2 months follow-up) for patients with ROS1-rearranged advanced NSCLC from PROFILE 1001.

Patients and methods: ROS1 status was determined by FISH or reverse transcriptase-polymerase chain reaction. All patients received crizotinib at a starting dose of 250 mg twice daily.

Results: Fifty-three patients received crizotinib, with a median duration of treatment of 22.4 months. At data cut-off, treatment was ongoing in 12 patients (23%). The objective response rate (ORR) was 72% [95% confidence interval (CI), 58% to 83%], including six confirmed complete responses and 32 confirmed partial responses; 10 patients had stable disease. Responses were durable (median duration of response 24.7 months; 95% CI, 15.2-45.3). ORRs were consistent across different patient subgroups. Median progression-free survival was 19.3 months (95% CI, 15.2-39.1). A total of 26 deaths (49%) occurred (median follow-up period of 62.6 months), and of the remaining 27 patients (51%), 14 (26%) were in follow-up at data cut-off. Median OS was 51.4 months (95% CI, 29.3 to not reached) and survival probabilities at 12, 24, 36, and 48 months were 79%, 67%, 53%, and 51%, respectively. No correlation was observed between OS and specific ROS1 fusion partner. Treatment-related adverse events (TRAEs) were mainly grade 1 or 2, per CTCAE v3.0. There were no grade ≥4 TRAEs and no TRAEs associated with permanent discontinuation. No new safety signals were reported with long-term crizotinib treatment.

Conclusions: These findings serve as a new benchmark for OS in ROS1-rearranged advanced NSCLC, and continue to show the clinically meaningful benefit and safety of crizotinib in this molecular subgroup.

Trial registration number: ClinicalTrials.gov identifier NCT00585195.

Keywords: ROS1; crizotinib; non-small-cell lung cancer; overall survival.

Figure 1.

Overall survival. Shown is the Kaplan–Meier curve estimating overall survival (OS) among the 53 ROS1-positive NSCLC patients treated with crizotinib in PROFILE 1001. After a median follow-up of 62.6 months, median OS was 51.4 months. Vertical lines on the curve indicate censoring of data.

Figure 2.

Overall survival and ROS1 fusion partners. Shown is overall survival (OS) for the 30 patients who underwent testing for ROS1 fusion partners. Patients are grouped according to ROS1 fusion partner, shown on the left. Asterisks indicate censored patients. One patient was identified as positive for both ROS1 and ALK rearrangement by FISH testing, but next-generation sequencing (NGS) revealed only an EML4-ALK fusion and no ROS1 rearrangement (triangle). One patient was identified as positive for ROS1 rearrangement by FISH testing, but had an atypical FISH pattern, and NGS subsequently revealed normal, non-rearranged ROS1 (circle).