Characterizing tumor responses from RAINBOW, a randomized phase III trial of ramucirumab (RAM) plus paclitaxel (PAC) vs placebo (PBO) plus PAC in patients (pts) with previously treated advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma.

Abstract

45 Background: In RAINBOW, OS and PFS were improved for pts with previously treated gastric/GEJ adenocarcinoma in the RAM + PAC arm. Objective response rate was also significantly improved: 28% (92/330) RAM + PAC vs 16% (54/335) PBO + PAC (P =.0001). Timing and duration of responses and quality of life (QoL) are described. Methods: Patients were randomized 1:1 to RAM 8 mg/kg or PBO on days 1 and 15 + PAC 80 mg/m2 on days 1, 8, and 15 (28-day cycle). Radiographic assessment of disease per RECIST v1.1 and assessment of QoL with the EORTC QLQ-C30 were done at baseline and 6-wk intervals following the first dose of study therapy. Time to response (TTR) was the time from randomization to first tumor response (complete or partial). Duration of response (DoR) was the time from first tumor response to disease progression. A swimmer plot of DoR, survival, and status at study end was developed. Time-to-event curves were generated using the Kaplan-Meier method. Hazard ratio (HR) for DoR was generated from a stratified Cox model. QoL scores were classified as improved or worsened if change from baseline was ≥ 10 points (100-point scale), otherwise considered stable. Results: Median TTR was 6.7 wks (range 4.3-33.3) for RAM + PAC pts and 6.6 wks (5.1-37.1) for PBO + PAC pts. A detailed swimmer plot confirms a majority of RAM + PAC pts (58% [53/92]) and PBO + PAC pts (61% [33/54]) responded by the first 6-wk assessment. Of these responders, 11% (6/53) and 6% (2/33) were still responding at 12 mos. Median DoR was 4.4 mos (95% CI 4.1, 5.5) in the RAM + PAC arm and 2.8 mos (95% CI 2.1, 4.2) in the PBO + PAC arm (HR = 0.66, 95% CI 0.45, 0.97; P =.0332). At 6 wks, rates of improved/stable QoL scores among responders were similar between treatment arms and higher among the responders (73% RAM + PAC vs 74% PBO + PAC) than in the intent-to-treat population (53% vs 50%). Conclusions: Patients with advanced gastric/GEJ cancer not only showed an improved response rate with RAM + PAC, but responses were also more durable. For the majority of pts, response occurred within the first 6 wks of therapy and was associated with QoL benefit. Clinical trial information: NCT01170663.