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

Cancer Res Treat. 2018 Jul;50(3):691-700. doi: 10.4143/crt.2017.280. Epub 2017 Jul 6.

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.

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

Publication types

  • Clinical Trial, Phase III
  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Anaplastic Lymphoma Kinase
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Crizotinib
  • Docetaxel
  • Drug Administration Schedule
  • Female
  • Humans
  • Intention to Treat Analysis
  • Kaplan-Meier Estimate
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / genetics
  • Male
  • Pemetrexed / administration & dosage*
  • Pemetrexed / adverse effects
  • Pyrazoles / administration & dosage*
  • Pyrazoles / adverse effects
  • Pyridines / administration & dosage*
  • Pyridines / adverse effects
  • Receptor Protein-Tyrosine Kinases / genetics*
  • Survival Analysis
  • Taxoids / administration & dosage*
  • Taxoids / adverse effects
  • Treatment Outcome

Substances

  • Pyrazoles
  • Pyridines
  • Taxoids
  • Pemetrexed
  • Docetaxel
  • Crizotinib
  • ALK protein, human
  • Anaplastic Lymphoma Kinase
  • Receptor Protein-Tyrosine Kinases