Quality-of-life and performance status results from the phase III RAINBOW study of ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated gastric or gastroesophageal junction adenocarcinoma

Abstract

Background: The phase III RAINBOW trial demonstrated that the addition of ramucirumab to paclitaxel improved overall survival, progression-free survival, and tumor response rate in fluoropyrimidine-platinum previously treated patients with advanced gastric/gastroesophageal junction (GEJ) adenocarcinoma. Here, we present results from quality-of-life (QoL) and performance status (PS) analyses.

Patients and methods: Patients with Eastern Cooperative Oncology Group PS of 0/1 were randomized to receive ramucirumab (8 mg/kg i.v.) or placebo on days 1 and 15 of a 4-week cycle, with both arms receiving paclitaxel (80 mg/m(2)) on days 1, 8, and 15. Patient-reported outcomes were assessed with the QoL/health status questionnaires EORTC QLQ-C30 and EQ-5D at baseline and 6-week intervals. PS was assessed at baseline and day 1 of every cycle. Time to deterioration (TtD) in each QLQ-C30 scale was defined as randomization to first worsening of ≥10 points (on 100-point scale) and TtD in PS was defined as first worsening to ≥2. Hazard ratios (HRs) for treatment effect were estimated using stratified Cox proportional hazards models.

Results: Of the 665 patients randomized, 650 (98%) provided baseline QLQ-C30 and EQ-5D data, and 560 (84%) also provided data from ≥1 postbaseline time point. Baseline scores for both instruments were similar between arms. Of the 15 QLQ-C30 scales, 14 had HR < 1, indicating similar or longer TtD in QoL for ramucirumab + paclitaxel. Treatment with ramucirumab + paclitaxel was also associated with a delay in TtD in PS to ≥2 (HR = 0.798, P = 0.0941). Alternate definitions of PS deterioration yielded similar results: PS ≥ 3 (HR = 0.656, P = 0.0508), deterioration by ≥1 PS level (HR = 0.802, P = 0.0444), and deterioration by ≥2 PS levels (HR = 0.608, P = 0.0063). EQ-5D scores were comparable between treatment arms, stable during treatment, and worsened at discontinuation.

Conclusion: In patients with previously treated advanced gastric/GEJ adenocarcinoma, addition of ramucirumab to paclitaxel prolonged overall survival while maintaining patient QoL with delayed symptom worsening and functional status deterioration.

Clinicaltrialsgov: NCT01170663.

Keywords: EORTC QLQ-C30; EQ-5D; GEJ cancer; gastric cancer; quality of life; ramucirumab.

Figure 1.

Time to deterioration in EORTC QLQ-C30 scales. Hazard ratios are shown for time to deterioration for each of the EORTC QLQ-C30 scales in the ramucirumab + paclitaxel group, when compared with the placebo + paclitaxel arm. Horizontal bars represent 95% confidence limits. CI, confidence interval; HR, hazard ratio; N, number of patients with deterioration; PBO, placebo; PTX, paclitaxel; RAM, ramucirumab.

Figure 2.

(A–D) Kaplan–Meier plots of time to deterioration of performance status. Time to deterioration defined as a decline in ECOG PS: (A) to ≥2; (B) to ≥3; (C) by ≥1 level; (D) by ≥2 levels. The y-axis shows the probability that patients will not deteriorate to these specific PS thresholds. Median TtD (months) is shown, along with the total number of patients, the number of TtD events and the number of censored patients. NA, not available; PS, Eastern Cooperative Oncology Group performance status; TtD, time to deterioration.