Reduced-Intensity Oxaliplatin/Capecitabine for Older and Frail Patients With Advanced Gastroesophageal Cancer

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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.

Study Details

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:

  • The CHEMO-INTENSITY pathway randomly assigned 514 patients to receive oxaliplatin/capecitabine at dose level A (n = 170; oxaliplatin at 130 mg/m2 on day 1, capecitabine at 625 mg/m2 twice daily on days 1–21 in 21-day cycles), level B (n = 171; doses 0.8 times level A), or level C (n = 173; doses 0.6 times level A).
  • The CHEMO-BSC pathway randomly assigned 45 patients with patient and clinician agreement that the indication for chemotherapy was uncertain to level C (n = 23) vs best supportive care (n = 22).

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.

Key Findings

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

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