Exploratory analysis of safety by histology and efficacy in a nonsquamous NSCLC subgroup in REVEL: A randomized phase III study of ramucirumab (RAM) plus docetaxel (DOC) vs DOC for second-line treatment of stage IV non-small-cell lung cancer (NSCLC).

8055 Background: REVEL, a study inclusive of nonsquamous (NSQ) and squamous (SQ) NSCLC, led to FDA approval of second-line RAM+DOC for patients (pts) with metastatic NSCLC based on improved survival. Neutropenia, febrile neutropenia, gastrointestinal and pulmonary hemorrhage events were similar across histologies. Additional outcomes are presented. Methods: A total of 1,253 pts with SQ or NSQ NSCLC received DOC (75 mg/m2) plus RAM (10 mg/kg; N = 628) or placebo (N = 625) after disease progression on platinum-based therapy (NCT01168973). Endpoints evaluated in specified histologic subgroups were OS, PFS, response rates, safety, and QoL. OS and PFS were analyzed using Kaplan-Meier (KM) method and Cox proportional hazard model. Response was compared using the Cochran-Mantel-Haenszel test. The primary QoL analysis was time to deterioration (TtD) of the Lung Cancer Symptom scale (LCSS) using the KM method. Results: Of the 73% (N = 912) of NSQ tumors, the majority were adenocarcinoma (79%; N = 725). Efficacy outcomes for pts with adenocarcinoma were similar to the NSQ population (see table). Incidences of pts with ≥ 1 treatment-emergent adverse event (TEAE), ≥ 1 serious adverse event, TEAEs grade ≥ 3, and TEAEs leading to dose adjustment or discontinuation were similar between treatment arms and across NSQ and SQ histologies. The TtD for total LCSS score was similar between treatment arms in NSQ and SQ subgroups. Conclusions: REVEL demonstrated an acceptable benefit/risk profile for RAM+DOC, with favorable efficacy and manageable safety outcomes seen across the major histologic subtypes of NSCLC. Clinical trial information: NCT01168973. NSQ ITT NSQ Adenocarcinoma RAM+DOC (N = 465) PBO+DOC (N = 447) HR (95% CI) RAM+DOC (N = 377) PBO+DOC (N = 348) HR (95% CI) Median OS, mos 11.1 9.7 0.83 (0.71, 0.97) 11.2 9.8 0.83 (0.69, 0.99) Median PFS, mos 4.6 3.7 0.77 (0.67, 0.88) 4.5 3.9 0.75 (0.64, 0.88) DCR (CR+PR+SD), % 66 55 65 56 ORR (CR+PR), % 22 15 19 15 CR = complete response; DCR = disease control rate; HR = hazard ratio; ITT = intent-to-treat; ORR = overall response; PBO = placebo; PR = partial response; SD = stable disease.