Cancer Res Treat.  2018 Jul;50(3):691-700. 10.4143/crt.2017.280.

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

• Nishio M
• Kim DW
• Wu YL
• Nakagawa K
• Solomon BJ
• Shaw AT
• Hashigaki
• Ohki E
• Usari T
• Paolini J
• Polli A
• Wilner KD
• Mok T

• KMID: 2417858
• DOI: http://doi.org/10.4143/crt.2017.280

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, open-label 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.

Keyword

Asia; Carboplatin; Cisplatin; Crizotinib; Non-small cell lung carcinoma; Pemetrexed

MeSH Terms

Asia
Asian Continental Ancestry Group*
Carboplatin
Carcinoma, Non-Small-Cell Lung*
Cisplatin
Continental Population Groups
Diarrhea
Disease-Free Survival
Drug Therapy*
Humans
Incidence
Lymphoma
Nausea
Pemetrexed
Phosphotransferases
Vision Disorders
Carboplatin
Cisplatin
Pemetrexed
Phosphotransferases

Figure

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  Fig. 1. Progression-free survival by independent radiology review for all previously treated patients (A); previously treated Asian patients (B); previously treated non-Asian patients (C); all previously untreated patients (D); previously untreated Asian patients (E); and previously untreated non-Asian patients (F). mPFS, median progression-free survival; CI, confidence interval; HR, hazard ratio; ECOG PS, Eastern Cooperative Oncology Group performance status. a)Based on the Brookmeyer and Crowley method, b)Based on the Cox proportional hazards model (assuming proportional hazards, an HR < 1 indicates a reduction in hazard rate in favor of crizotinib; an HR > 1 indicates a reduction in hazard rate in favor of chemotherapy), c)One-sided p-value from the log-rank test stratified by ECOG PS, brain metastases, and prior epidermal growth factor receptor tyrosine kinase inhibitor treatment (PROFILE 1007) or by ECOG PS, race, and brain metastases (PROFILE 1014), d)One-sided p-value from the unstratified log-rank test.

Reference

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