East Asian Subgroup Analysis of a Randomized, Double-Blind, Phase 3 Study of Docetaxel and Ramucirumab Versus Docetaxel and Placebo in the Treatment of Stage IV Non-small Cell Lung Cancer Following Disease Progression after One Prior Platinum-Based Therapy (REVEL)

Abstract

PurposeREVEL demonstrated improved overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) with docetaxel+ramucirumab versus docetaxel+placebo in 1,253 intent-to-treat (ITT) stage IV non-small cell lung cancer patients with disease progression following platinum-based chemotherapy. Results from the East Asian subgroup analysis are reported.Materials and MethodsSubgroup analyses were performed in the East Asian ITT population (n=89). Kaplan-Meier analysis and Cox proportional hazards regression were performed for OS and PFS, and the Cochran-Mantel-Haenszel test was performed for response rate.ResultsIn docetaxel+ramucirumab (n=43) versus docetaxel+placebo (n=46), median OS was 15.44 months versus 10.17 months (hazard ratio [HR], 0.762; 95% confidence interval [CI], 0.444 to 1.307), median PFS was 4.88 months versus 2.79 months (HR, 0.658; 95% CI, 0.408 to 1.060), and ORR was 25.6% (95% CI, 13.5 to 41.2) versus 8.7% (95% CI, 2.4 to 20.8). Due to increased incidence of neutropenia and febrile neutropenia in East Asian patients, starting dose of docetaxel was reduced for newly enrolled East Asian patients (75 to 60 mg/m2, n=24). In docetaxel+ramucirumab versus docetaxel+placebo, incidence of neutropenia was 84.4% versus 72.7% (75 mg/m2) and 54.5% versus 38.5% (60 mg/m2). Incidence of febrile neutropenia was 43.8% versus 12.1% (75 mg/m2) and 0% versus 7.7% (60 mg/m2).ConclusionResults of this subgroup analysis showed a trend favoring ramucirumab+docetaxel for median OS, PFS, and improved ORR in East Asian patients, consistent with ITT population results. Reduction of starting dose of docetaxel in East Asian patients was associated with improved safety.

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

“…In contrast, the incidence of these AEs was similar in previously untreated Asian and non-Asian patients, although the incidence of constipation was higher among Asian patients in PROFILE 1014. The higher incidence of AEs among Asian patients than non-Asian patients noted in PROFILE 1007 is consistent with previous reports for crizotinib [ 11 ] and chemotherapy [ 12 ].…”

Ramucirumab Safety in East Asian Patients: A Meta-Analysis of Six Global, Randomized, Double-Blind, Placebo-Controlled, Phase III Clinical Trials

“… 6 The decrement of docetaxel starting dose from 75 mg/m 2 to 60 mg/m 2 in EA patients reduced the incidence of neutropenia and febrile neutropenia to a rate similar to that observed for non-EA patients. 13 …”

“… 11 - 14 Overall, ramucirumab treatment conferred benefits to EA patients in terms of prolonging median survival times, improving progression-free survival, and increasing response rate. 11 - 13 As for safety, EA patients have been reported to exhibit a higher incidence of certain adverse events (AEs) compared with non-EA patients. 3 - 8 For instance, subgroup analyses from the RAINBOW and REVEL trials indicated higher incidence rates of any-grade neutropenia in ramucirumab-treated EA patients compared with those in the non-EA population (RAINBOW, 78% EA v 43% non-EA; REVEL, 84.4% EA v 53.4% non-EA).…”

Overexpression of GPR35 confers drug resistance in NSCLC cells by β-arrestin/Akt signaling

“…Among these, platinum agent is the first-line chemodrugs combined with other cytotoxic agents, such as docetaxel and paclitaxel. 4 , 5 However, due to frequent chemoresistance, the effective treatment remains a critical challenge.…”