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

Abstract

PurposeCrizotinib 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 MethodsThis 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.ResultsIn 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.ConclusionThese 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.

Front‐line treatment of ceritinib improves efficacy over crizotinib for Asian patients with anaplastic lymphoma kinase fusion NSCLC: The role of systemic progression control

“…Nishio et al reported a PFS of 13.6 months and a 56% hazard reduction of disease progression and death for Asian patients in the PROFILE 1014 compared to a PFS of 9.6 months and a 48% hazard reduction for non-Asian patients in the same study. 24 Taken together, the present study demonstrated a good efficacy of ceritinib and crizotinib treatment for Asian Taiwanese patients with ALK-positive NSCLC, with a superior efficacy in favor of ceritinib treatment.…”

Emerging therapies for non-small cell lung cancer

“…For patients with brain metastasis at baseline in ALTA trial, brigatinib achieved potent efficacy with a progression risk reduction of 73%. Similar adverse events were identified compared to previous ALK-TKI [89,97,[126][127][128]. Most importantly, the final PFS and OS result of brigatinib should be expected to decipher whether brigatinib might be superior to the new standard first-line alectinib.…”

Real-World Treatment Patterns, Survival, and Prediction of CNS Progression in ALK-Positive Non-Small-Cell Lung Cancer Patients Treated with First-Line Crizotinib in Latin America Oncology Practices

“…In a retrospective study conducted by Cadranel et al [20], no difference was found when comparing populations across the USA and Korea in terms of OS and physician-defined PFS, even after discontinuation of crizotinib. A subsequent pooled analysis of the Asian subset of patients in both the PROFILE 1007 and PROFILE 1014 trials concluded that the effect in terms of PFS is maintained in both Asian and non-Asian patients [25], adding to the body of evidence that the benefit of anti-ALK therapy is present in multiple populations. This hypothesis was further validated for individual cohorts in China [26], the USA [24], Korea [27], and India [28].…”