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

S-E Al-Batran, E Van Cutsem, S C Oh, G Bodoky, Y Shimada, S Hironaka, N Sugimoto, O N Lipatov, T-Y Kim, D Cunningham, P Rougier, K Muro, A M Liepa, K Chandrawansa, M Emig, A Ohtsu, H Wilke, S-E Al-Batran, E Van Cutsem, S C Oh, G Bodoky, Y Shimada, S Hironaka, N Sugimoto, O N Lipatov, T-Y Kim, D Cunningham, P Rougier, K Muro, A M Liepa, K Chandrawansa, M Emig, A Ohtsu, H Wilke

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.

© The Author 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology.

Figures

Figure 1.
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.
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.

References

    1. Ferlay J, Soerjomataram I, Ervik M et al. . GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11 [Internet]. Lyon, France: International Agency for Research on Cancer; 2013. , accessed on 16 May 2015.
    1. Price TJ, Shapiro JD, Segelov E et al. . Management of advanced gastric cancer. Expert Rev Gastroenterol Hepatol 2012; 6: 199–209.
    1. Thuss-Patience PC, Kretzschmar A, Bichev D et al. . Survival advantage for irinotecan versus best supportive care as second-line chemotherapy in gastric cancer—a randomised phase III study of the Arbeitsgemeinschaft Internistische Onkologie (AIO). Eur J Cancer 2011; 47: 2306–2314.
    1. Kang JH, Lee SI, Lim DH et al. . Salvage chemotherapy for pretreated gastric cancer: a randomized phase III trial comparing chemotherapy plus best supportive care with best supportive care alone. J Clin Oncol 2012; 30: 1513–1518.
    1. Ford HER, Marshall A, Bridgewater JA et al. . Docetaxel versus active symptom control for refractory oesophagogastric adenocarcinoma (COUGAR-02): an open-label, phase 3 randomised controlled trial. Lancet Oncol 2014; 15: 78–86.
    1. Fuchs CS, Tomasek J, Yong CJ et al. . Ramucirumab monotherapy for previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (REGARD): an international, randomised, multicenter, placebo-controlled, phase 3 trial. Lancet 2014; 383: 31–39.
    1. Spratlin JL, Cohen RB, Eadens M et al. . Phase I pharmacologic and biologic study of ramucirumab (IMC-1121B), a fully human immunoglobulin G1 monoclonal antibody targeting the vascular endothelial growth factor receptor-2. J Clin Oncol 2010; 28: 780–787.
    1. Wilke H, Muro K, Van Cutsem E et al. . Ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (RAINBOW): a double-blind, randomised phase 3 trial. Lancet Oncol 2014; 15: 1224–1235.
    1. Wilke H, Van Cutsem E, Oh SC et al. . RAINBOW: A global, phase III randomized, double-blind study of ramucirumab plus paclitaxel versus placebo plus paclitaxel in the treatment of metastatic gastroesophageal junction (GEJ) and gastric adenocarcinoma following disease progression on first-line platinum- and fluoropyrimidine-containing combination therapy. J Clin Oncol 2014; 32(suppl 3): abstr LBA7.
    1. Al-Batran SE, Ajani JA. Impact of chemotherapy on quality of life in patients with metastatic esophagogastric cancer. Cancer 2010; 116: 2511–2518.
    1. Satoh T, Bang YJ, Gotovkin EA et al. . Quality of life in the trastuzumab for gastric cancer trial. Oncologist 2014; 19: 712–719.
    1. Aaronson NK, Ahmedzai S, Bergman B et al. . The European Organization for Research and Treatment QLQ-C30: a quality-of-life instrument for use in international clinical trials in oncology. J Natl Cancer Inst 1993; 85: 365–376.
    1. EuroQol Group. EuroQol—a new facility for the measurement of health-related quality of life. Health Policy 1990; 16: 199–208.
    1. Oken MM, Creech RH, Tormey DC et al. . Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol 1982; 5: 649–655.
    1. Fayers PM, Aaronson NK, Bjordal K et al. . on behalf of the EORTC Quality of Life Group. EORTC QLQ-C30 Scoring Manual, 3rd Edition European Organisation for Research and Treatment of Cancer. Brussels: EORTC, 2001. ISBN: 2-9300 64-22-6.
    1. Osoba D, Rodrigues G, Myles J et al. . Interpreting the significance of changes in health-related quality-of-life scores. J Clin Oncol 1998; 16: 139–144.
    1. Cox DR, Snell EJ. Analysis of Binary Data, 2nd edition Chapman & Hall: London, 1989.
    1. Dolan P. Modeling valuations for EuroQol health states. Med Care 1997; 35: 1095–1108.
    1. Al-Batran SE, Hozaeel W, Tauchert FK et al. . The impact of docetaxel-related toxicities on health-related quality of life in patients with metastatic cancer (QoliTax). Ann Oncol 2015; 26: 1244–1248.

Source: PubMed

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