Dataset Information

Early Weight Loss as a Prognostic Factor in Patients with Advanced Gastric Cancer: Analyses from REGARD, RAINBOW, and RAINFALL Phase III Studies.

ABSTRACT:

Background

Weight loss is common in advanced gastric and gastroesophageal junction adenocarcinoma (G/GEA); however, the prognostic implications of weight loss during the first cycle (C1) of chemotherapy remain poorly characterized. In this study, we investigated the impact of early weight loss during systemic treatment as a potential prognostic factor for overall survival (OS) in patients with advanced G/GEA.

Materials and methods

We performed a post hoc analysis of three phase III studies of ramucirumab. Patients were categorized into two groups: weight loss of ≥3% and <3% based on weight change during C1 (3-4 weeks) of treatment. OS by weight groups was assessed for each study and as a pooled meta-analysis. The effect of C1 weight change on patient survival was evaluated using univariate and multivariate Cox models.

Results

A total of 1,464 patients with weight data at the end of C1 were analyzed: REGARD (n = 311), RAINBOW (n = 591), and RAINFALL (n = 562). For all three studies, there were fewer patients in the weight loss ≥3% than <3% group. OS was numerically shorter for patients with weight loss of ≥3% than for patients with weight loss of <3% during C1 irrespective of treatment arm. Similar treatment independent effects of early weight loss on OS were observed in the meta-analysis. Overall, early weight loss ≥3% was associated with shorter survival in patients receiving active drug as well as placebo/best supportive care.

Conclusion

This large post hoc analysis demonstrated that weight loss of ≥3% during C1 was a negative prognostic factor for OS in patients with advanced G/GEA.

Implications for practice

This comprehensive analysis examining early weight loss during systemic treatment as a predictor of survival outcomes in patients with advanced gastric and gastroesophageal junction adenocarcinoma (G/GEA) includes a large sample size, reliable on-treatment data reported in well-conducted phase III clinical trials, and global representation of cancer patients with advanced G/GEA. Understanding the impact of on-treatment weight loss is clinically relevant and may represent an opportunity for targeted interventions.

SUBMITTER: Mansoor W

PROVIDER: S-EPMC8417853 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:PurposeTo identify baseline prognostic factors for survival in patients with disease progression, during or after chemotherapy for the treatment of advanced gastric or gastroesophageal junction (GEJ) cancer.Materials and methodsWe pooled data from patients randomized between 2009 and 2012 in 2 phase III, global double-blind studies of ramucirumab for the treatment of advanced gastric or GEJ adenocarcinoma following disease progression on first-line platinum- and/or fluoropyrimidine-containing therapy (REGARD and RAINBOW). Forty-one key baseline clinical and laboratory factors common in both studies were examined. Model building started with covariate screening using univariate Cox models (significance level=0.05). A stepwise multivariable Cox model identified the final prognostic factors (entry+exit significance level=0.01). Cox models were stratified by treatment and geographic region. The process was repeated to identify baseline prognostic quality of life (QoL) parameters.ResultsOf 1,020 randomized patients, 953 (93%) patients without any missing covariates were included in the analysis. We identified 12 independent prognostic factors of poor survival: 1) peritoneal metastases; 2) Eastern Cooperative Oncology Group (ECOG) performance score 1; 3) the presence of a primary tumor; 4) time to progression since prior therapy <6 months; 5) poor/unknown tumor differentiation; abnormally low blood levels of 6) albumin, 7) sodium, and/or 8) lymphocytes; and abnormally high blood levels of 9) neutrophils, 10) aspartate aminotransferase (AST), 11) alkaline phosphatase (ALP), and/or 12) lactate dehydrogenase (LDH). Factors were used to devise a 4-tier prognostic index (median overall survival [OS] by risk [months]: high=3.4, moderate=6.4, medium=9.9, and low=14.5; Harrell's C-index=0.66; 95% confidence interval [CI], 0.64-0.68). Addition of QoL to the model identified patient-reported appetite loss as an independent prognostic factor.ConclusionsThe identified prognostic factors and the reported prognostic index may help clinical decision-making, patient stratification, and planning of future clinical studies.

Project description:BackgroundIn 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 methodsTumor 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.ResultsIn 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.ConclusionTreatment 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 practiceRamucirumab 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.

Project description:Background and objectiveGastric cancer has been associated with notable geographic heterogeneity in previous multi-regional studies. In particular, patients from Japan have better outcomes compared with patients from other regions. Here, we assess patient-focused outcomes for the subgroup of Japanese patients in the global RAINBOW study.MethodsQuality of life (QoL) was assessed using the European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire-Core 30 (QLQ-C30) at baseline and 6-week intervals. Investigators assessed performance status before each 4-week cycle. Time-to-deterioration in each QLQ-C30 scale was defined as randomization to first worsening of ≥ 10 points (on a 100-point scale). Time-to-deterioration in performance status was defined as first worsening to ≥ 2. Hazard ratios were estimated using Cox proportional hazards models.ResultsThe Japan subgroup contained 140 patients (ramucirumab plus paclitaxel, n = 68; placebo plus paclitaxel, n = 72); baseline QoL data were available for all patients. At baseline, QLQ-C30 scores were similar between study arms. Of the 15 QLQ-C30 scales, nine had a hazard ratio < 1, indicating similar or numerically longer time-to-deterioration in QoL for ramucirumab plus paclitaxel; all 95% confidence intervals included 1. Best mean change from baseline numerically favored ramucirumab plus paclitaxel in most QoL scales. The hazard ratios for time-to-deterioration of performance status to ≥ 2 were 0.64 in the Japan subgroup and 0.88 in the non-Asian subgroup. The Japan subgroup had better QoL at baseline compared with the non-Asian subgroup.ConclusionsTreatment with ramucirumab plus paclitaxel maintained QoL and performance status over time compared with placebo plus paclitaxel in the Japan subgroup of the RAINBOW trial. These data suggest that the heterogeneity in gastric cancer between geographic regions includes multiple measures of QoL.Trial registration numberNCT01170663 (first submitted 21 July, 2010).