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Crizotinib versus Chemotherapy in Asian Patients with ALK-Positive Advanced Non-small Cell Lung Cancer.

ABSTRACT: Purpose:Crizotinib has demonstrated superior progression-free survival (PFS) and objective response rates (ORRs) versus chemotherapy in previously treated and untreated patients with anaplastic lymphoma kinase (ALK)-positive advanced non-small cell lung cancer (NSCLC). We report the safety and efficacy of crizotinib in Asian subpopulations of two global phase III trials. Materials and Methods:This analysis evaluated previously treated and untreated patients in two randomized, openlabel phase III trials of crizotinib versus chemotherapy in ALK-positive advanced NSCLC in second-line (PROFILE 1007) and first-line settings (PROFILE 1014). Efficacy and safety were analyzed by race in the intention-to-treat and "as-treated" populations for efficacy and safety endpoints, respectively. Results:In previously treated (n=157) and untreated (n=157) Asian patients, PFS was statistically significantly longer with crizotinib versus chemotherapy (hazard ratio for PFS, 0.526; 95% confidence interval, 0.363 to 0.762; p < 0.001 and hazard ratio, 0.442; 95% confidence interval, 0.302 to 0.648; p < 0.001, respectively). Similar antitumor activity was seen in the non-Asian and overall populations. ORRs were statistically significantly higher with crizotinib versus chemotherapy in both Asian and non-Asian previously treated and untreated patients (p < 0.05). The most common treatment-emergent adverse events (any grade)with crizotinib were vision disorder, diarrhea, and nausea, which were observed at a comparable incidence across Asian and non-Asian populations, irrespective of previous treatment status. Most adverse events were mild to moderate in severity. Conclusion:These data, currently the only analysis showing Asian and non-Asian populations in the same study, support the efficacy and safety of crizotinib in Asian patients with previously treated or untreated ALK-positive advanced NSCLC.

SUBMITTER: Nishio M

PROVIDER: S-EPMC6056984 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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Crizotinib versus Chemotherapy in Asian Patients with ALK-Positive Advanced Non-small Cell Lung Cancer.

Nishio Makoto M Kim Dong-Wan DW Wu Yi-Long YL Nakagawa Kazuhiko K Solomon Benjamin J BJ Shaw Alice T AT Hashigaki Satoshi S Ohki Emiko E Usari Tiziana T Paolini Jolanda J Polli Anna A Wilner Keith D KD Mok Tony T

Cancer research and treatment 20170706 3

<h4>Purpose</h4>Crizotinib has demonstrated superior progression-free survival (PFS) and objective response rates (ORRs) versus chemotherapy in previously treated and untreated patients with anaplastic lymphoma kinase (ALK)-positive advanced non-small cell lung cancer (NSCLC). We report the safety and efficacy of crizotinib in Asian subpopulations of two global phase III trials.<h4>Materials and methods</h4>This analysis evaluated previously treated and untreated patients in two randomized, open ...[more]

PMID: 28701030

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Project description:Background:This is the first trial to directly compare efficacy and safety of alectinib versus standard chemotherapy in advanced/metastatic anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer (NSCLC) patients who have progressed on, or were intolerant to, crizotinib. Patients and methods:ALUR (MO29750; NCT02604342) was a randomized, multicenter, open-label, phase III trial of alectinib versus chemotherapy in advanced/metastatic ALK-positive NSCLC patients previously treated with platinum-based doublet chemotherapy and crizotinib. Patients were randomized 2 : 1 to receive alectinib 600?mg twice daily or chemotherapy (pemetrexed 500?mg/m2 or docetaxel 75?mg/m2, both every 3?weeks) until disease progression, death, or withdrawal. Primary end point was investigator-assessed progression-free survival (PFS). Results:Altogether, 107 patients were randomized (alectinib, n?=?72; chemotherapy, n?=?35) in 13 countries across Europe and Asia. Median investigator-assessed PFS was 9.6?months [95% confidence interval (CI): 6.9-12.2] with alectinib and 1.4?months (95% CI: 1.3-1.6) with chemotherapy [hazard ratio (HR) 0.15 (95% CI: 0.08-0.29); P?<?0.001]. Independent Review Committee-assessed PFS was also significantly longer with alectinib [HR 0.32 (95% CI: 0.17-0.59); median PFS was 7.1?months (95% CI: 6.3-10.8) with alectinib and 1.6?months (95% CI: 1.3-4.1) with chemotherapy]. In patients with measurable baseline central nervous system (CNS) disease (alectinib, n?=?24; chemotherapy, n?=?16), CNS objective response rate was significantly higher with alectinib (54.2%) versus chemotherapy (0%; P?<?0.001). Grade ?3 adverse events were more common with chemotherapy (41.2%) than alectinib (27.1%). Incidence of AEs leading to study-drug discontinuation was lower with alectinib (5.7%) than chemotherapy (8.8%), despite alectinib treatment duration being longer (20.1?weeks versus 6.0?weeks). Conclusion:Alectinib significantly improved systemic and CNS efficacy versus chemotherapy for crizotinib-pretreated ALK-positive NSCLC patients, with a favorable safety profile. Trial registration:ClinicalTrials.gov NCT02604342; Roche study MO29750.

Project description:ObjectivesFood 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 methodsClinical data of advanced ROS1+NSCLC patients treated with first-line crizotinib or platinum-pemetrexed chemotherapy between August 2010 and December 2017 were analyzed.ResultsSeventy-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).ConclusionsOur 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 versus Chemotherapy in Asian Patients with ALK-Positive Advanced Non-small Cell Lung Cancer.

Publications

Crizotinib versus Chemotherapy in Asian Patients with ALK-Positive Advanced Non-small Cell Lung Cancer.

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