Dataset Information

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.

SUBMITTER: Shaw AT

PROVIDER: S-EPMC6637370 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Publications

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

Shaw A T AT Riely G J GJ Bang Y-J YJ Kim D-W DW Camidge D R DR Solomon B J BJ Varella-Garcia M M Iafrate A J AJ Shapiro G I GI Usari T T Wang S C SC Wilner K D KD Clark J W JW Ou S-H I SI

Annals of oncology : official journal of the European Society for Medical Oncology 20190701 7

<h4>Background</h4>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.<h4>Patients and methods</h4>ROS1 status was determined by FISH or reverse transcriptase-polymerase chain reaction. All patients received ...[more]

PMID: 30980071

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Project description:OBJECTIVES:Food and Drug Administration (FDA) approved crizotinib for advanced ROS1-rearranged (ROS1+) non-small-cell lung cancer (NSCLC) patients due to a single-arm study PROFILE 1001. However, there is no direct comparison between crizotinib and platinum-pemetrexed chemotherapy. MATERIALS AND METHODS:Clinical data of advanced ROS1+NSCLC patients treated with first-line crizotinib or platinum-pemetrexed chemotherapy between August 2010 and December 2017 were analyzed. RESULTS:Seventy-seven patients were eligible, including 30 (39.0%) in the crizotinib group and 47 (61.0%) in the platinum-pemetrexed chemotherapy group. The median follow-up was 28.1 months (95% confidence interval [CI]: 19.2-39.0). The objective response rate (ORR) of crizotinib (86.7%, 95% CI: 73.3-96.7) was higher than that of platinum-pemetrexed chemotherapy (44.7%, 95% CI: 29.8-57.4, P < .001). The disease control rate (DCR) was 96.7% (95% CI: 90.0-100) in the crizotinib group and 85.1% (95% CI: 74.5-95.7) in the chemotherapy group (P = .140). Significantly longer progression-free survival (PFS) was observed in the patients treated with crizotinib (18.4 months, 95% CI: 6.4-30.3) versus platinum-pemetrexed chemotherapy (8.6 months, 95% CI: 6.9-10.3, P < .001). Overall survival (OS) was also compared between the two groups and no significant difference was seen (Not reach vs 28.4 months [95% CI: 20.7-36.0], P = .176). Notably, a total of 37 patients have treatment crossover after the failure of first-line treatment. Among those patients, difference in OS was not statistically significant between seven patients who have given first-line crizotinib (38.6 months, 95% CI: 0-81.0) and 30 patients who have given platinum-pemetrexed chemotherapy initially (32.8 months, 95% CI: 11.9-53.8, P = .805). CONCLUSIONS:Our results suggested that first-line crizotinib had higher ORR and longer PFS than platinum-pemetrexed chemotherapy in patients with advanced ROS1+NSCLC, but the differences were not observed for OS.

Dataset Information

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

Publications

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

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