Tumor Response and Symptom Palliation from RAINBOW, a Phase III Trial of Ramucirumab Plus Paclitaxel in Previously Treated Advanced Gastric Cancer

Abstract

Background: In the intent-to-treat (ITT) population of the RAINBOW study, objective response rate (ORR) was 28% and 16% in the ramucirumab and control arms, respectively. To further characterize tumor response, we present details on timing and extent of tumor shrinkage, as well as associations with symptom palliation.

Materials and methods: Tumor response was assessed with RECIST v1.1, and quality of life (QoL) was assessed with the European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire-Core 30 (EORTC QLQ-C30) v3.0. Prespecified and post hoc analyses were conducted in the ITT population, patients with measurable disease, or responders, and included best overall response (BOR), ORR, disease control rate (DCR), duration of response, time to response (TtR), change in tumor size, and associations of QoL with tumor shrinkage and BOR.

Results: In both treatment arms, median TtR was 1.5 months. Responses were more durable in the ramucirumab versus control arm (median 4.4 vs. 2.8 months). In patients with measurable disease (78% of ITT), ORR was 36% versus 20%; DCR was 81% versus 61% in the ramucirumab versus control arms. Waterfall plots demonstrated more tumor shrinkage in the ramucirumab versus control arm. Regardless of treatment, tumor response and stable disease were associated with improved or stable QoL, with more tumor shrinkage associated with greater symptom palliation.

Conclusion: Treatment with ramucirumab plus paclitaxel yielded the highest ORR reported to date for patients with previously treated advanced gastric or gastroesophageal junction adenocarcinoma. Additional details demonstrate robustness of tumor response results. The extent of tumor shrinkage is directly associated with symptom palliation and should be considered when evaluating patient needs and treatment selection. Clinical trial identification number. NCT01170663.

Implications for practice: Ramucirumab plus paclitaxel is a recognized standard of care as it improves survival for patients with advanced gastric or gastroesophageal junction adenocarcinoma who have been previously treated with recommended first-line therapy. These additional data on tumor response demonstrate a positive association between tumor shrinkage and symptom palliation in a patient population that is often symptomatic. These observations included patients with nonmeasurable disease, a group of patients often underrepresented in clinical trials. This knowledge can inform treatment decisions, which align individual patient characteristics and needs with demonstrated benefits.

Keywords: Gastric cancer; Gastroesophageal junction adenocarcinoma; Paclitaxel; Ramucirumab.

Conflict of interest statement

Disclosures of potential conflicts of interest may be found at the end of this article.

© 2020 AlphaMed Press.

Figures

Figure 1

Duration of response for patients with objective tumor response. Kaplan‐Meier analysis of the duration of response for patients from the RAINBOW study who had a complete or partial response in the ramucirumab (red line) versus the control (blue line) arms. Abbreviations: CI, confidence interval; HR, hazard ratio; PAC, paclitaxel; PBO, placebo; RAM, ramucirumab.

Figure 2

Time to and duration of tumor responses for patients with an objective response. The swimmer's plot characterizes the time to and duration of response (weeks) to ramucirumab plus paclitaxel (n = 92) (left panel) or to placebo plus paclitaxel (n = 54) (right panel) for each patient who achieved a complete or partial response in the RAINBOW trial.

Figure 3

Best percentage change in tumor size from baseline. The waterfall plot shows the best percentage change in the sum of tumor diameters measured at baseline and reassessed at least once postbaseline. Blue bars denote a sum of tumor diameters that decreased less than 30% from baseline. Red bars denote a sum of tumor diameters that decreased ≥30% from baseline, which is categorized as a complete or a partial response per RECIST v1.1. n = 238 in the ramucirumab plus paclitaxel arm, and n = 236 in the placebo plus paclitaxel arm. Note: from the ramucirumab arm and the control arm in the intent‐to‐treat population, 92 of 330 (28%) and 99 of 335 (30%) patients were not included in this figure. The most frequent reason for exclusion was nonmeasurable disease in 74 of 330 (22%) patients in the ramucirumab arm and 69 of 335 (21%) in the control arm. The second most common reason for exclusion was no postbaseline tumor assessment in 17 of 330 (5%) ramucirumab patients and 28 of 335 (8%) control patients. Less than 1% of patients in each treatment arm had no baseline tumor assessment.

Figure 4

Association of best percentage change in tumor size with best improvement in selected symptoms. Patient population is the same as that shown in the waterfall plots in Figure 3. Red bars are improved symptom scores, gray bars are stable or worsened symptom scores, white bars indicate patients who were not symptomatic at baseline, and black bars are patients who were not evaluable (without both a baseline and postbaseline assessment). Abbreviations: PAC, paclitaxel; PBO, placebo; RAM, ramucirumab.

Figure 5

Best improvement of global QoL and selected symptoms by best overall tumor response. All patients from the intent‐to‐treat population with best change in global QoL or symptoms (fatigue, pain, appetite loss) classified as improved, stable, deteriorated, or not evaluable are shown by their best overall tumor response. Best overall tumor response is denoted with blue bars for a CR or PR, orange bars for SD, gray bars for PD, and yellow indicates NE or not available. Not evaluable indicates that baseline and/or postbaseline assessment was not available. Abbreviations: CR, complete response; NE, not evaluable; PAC, paclitaxel; PBO, placebo; PD, progressive disease; PR, partial response; QoL, quality of life; RAM, ramucirumab; SD, stable disease.