Dataset Information

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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Publications

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:BackgroundThis 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 methodsALUR (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).ResultsAltogether, 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).ConclusionAlectinib significantly improved systemic and CNS efficacy versus chemotherapy for crizotinib-pretreated ALK-positive NSCLC patients, with a favorable safety profile.Trial registrationClinicalTrials.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.

Purpose

Materials and methods

Results

Conclusion

Publications

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

Similar Datasets

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