In the phase III GO2 trial reported in JAMA Oncology, Hall et al found that reduced-intensity oxaliplatin/capecitabine was associated with improved patient experience, reduced toxicity, and noninferior progression-free survival compared with higher-intensity treatment among older and frail patients with previously untreated locally advanced or metastatic gastroesophageal cancer.
The multicenter open-label noninferiority trial used nurse-led geriatric health assessment to recruit patients considered unsuited for full-dose combination chemotherapy on the basis of advanced age or frailty. Patients were enrolled between January 2014 and November 2017.
The study comprised two random assignment pathways:
Median age in all patient groups ranged from 76 to 79 years.
For the comparison among dose levels, the noninferiority boundary for progression-free survival for the lower doses vs level A was set at a hazard ratio of 1.34. Patient experience was assessed using overall treatment utility, which combines efficacy, toxic effects, quality of life (QoL), and patient value/acceptability (scored as good, intermediate, and poor). For CHEMO-BSC, the main outcome measure was overall survival.
In the CHEMO-INTENSITY random assignment, hazard ratios for progression free survival compared with dose level A were 1.09 (95% confidence interval [CI] = 0.89–1.32) for level B and 1.10 (95% CI = 0.90–1.33) for level C. Compared with level A, hazard ratios for overall survival were 1.09 (95% CI = 0.88–1.36) for level B and 1.14 (95% CI = 0.92–1.41) for level C. No subgroup was identified as having a clear progression-free or overall survival benefit with level A dosing.
On overall treatment utility assessment, patients in level C had more numerically good outcomes (43%) and fewer poor outcomes (29%) vs levels A and B at 9 weeks after starting chemotherapy (hazard ratio [HR] = 0.81, 95% CI = 0.54–1.19 for C vs A). Other patient experience outcomes also showed trends in favor of level C: time-to-deterioration of hazard ratio for C vs A was 0.88 (95% CI = 0.65–1.19) and global QoL (measured by the EORTC Quality of Life Questionnaire QLQ-C30 and EuroQoL-5 Dimension instrument scale) improved between baseline and 9 weeks with levels B and C, but not with level A. Cancer symptoms improved to a similar degree in all groups between baseline and 9 weeks.
During the first three 3-week cycles, dose reduction was required in 39%, 24%, and 13% of patients in the level A, B, and C groups, respectively, and discontinuation of treatment at least partly due to toxicity occurred in 33%, 29%, and 20%, respectively; 32%, 44%, and 58% completed the first three cycles without dose reduction or stoppage.
In the CHEMO-BSC pathway, median overall survival was 6.1 months in patients receiving level C dosing vs 3.0 months in those receiving best supportive care (HR = 0.69, 95% CI = 0.32–1.48, P = .34).
On multivariate analysis, baseline frailty, QoL, and neutrophil-to-lymphocyte ratio were independently associated with overall treatment utility and could be combined in a model for estimating the probability of differences in outcomes.
The investigators concluded, “This phase III randomized clinical trial found that reduced-intensity chemotherapy provided a better patient experience without significantly compromising cancer control and should be considered for older and/or frail patients. Baseline geriatric assessment can help predict the utility of chemotherapy but did not identify a group benefiting from higher-dose treatment.”
Matthew T. Seymour, MD, of the School of Medicine, University of Leeds, is the corresponding author for the JAMA Oncology article.
Disclosure: The study was supported by the National Institute for Health Research Clinical Research Network and Cancer Research UK. For full disclosures of the study authors, visit jamanetwork.com.The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.