2019 GI Cancers Symposium: Durvalumab, Tremelimumab, and Best Supportive Care vs Best Supportive Care Alone in Advanced, Refractory Colorectal Cancer
The phase II CCTG CO.26 trial evaluated whether the combination of durvalumab, a programmed cell death ligand 1 (PD-L1) inhibitor, and tremelimumab, an anti–cytotoxic T-lymphocyte–associated protein 4 (CTLA-4) antibody, plus best supportive care improved survival vs best supportive care alone in patients with advanced, refractory colorectal carcinoma. Findings from the study were presented by Chen et al at the 2019 Gastrointestinal Cancers Symposium (Abstract 481).
CCTG CO.26 Methods
Patients were eligible to enroll if they failed all standard regimens containing a fluoropyrimidine, irinotecan, and oxaliplatin (and an EGFR inhibitor if their disease was RAS wild-type).
Patients were randomly assigned 2:1 to receive the combination of durvalumab and tremelimumab plus best supportive care vs best supportive care alone. Patients in the combination arm received 75 mg of tremelimumab on day 1 of cycles 1 through 4 and 1,500 mg of durvalumab on day 1 every 28 days.
A total of 179 patients were randomly assigned between August 2016 and June 2017. About 85% of patients received at least 90% of planned doses of the combination therapy. The primary endpoint was overall survival.
Study Findings
The median follow-up was 15.2 months. Median overall survival was 6.6 months for durvalumab and tremelimumab plus best supportive care vs 4.1 months for best supportive care alone (hazard ratio [HR] = 0.72, 90% confidence interval (CI) = 0.54–0.97; P = .07).
Differences in progression-free survival were small—1.8 vs 1.9 months in the combination vs best supportive care groups, respectively (HR = 1.01, 90% CI = 0.76–1.34; P = .97). The disease control rate was 22.7% for the combination group vs 6.6% for best supportive care alone (P = .006).
Adverse events were more commonly reported in the durvalumab and tremelimumab plus best supportive care group—including grade 3/4 abdominal pain, fatigue, lymphocytosis, and eosinophilia—but there was less deterioration on EORTC QLQ-C30 physical function in the combination group. Since no patients with known defective mismatch repair tumors were enrolled in the study, confirmation of mismatch repair status is ongoing.
The authors concluded, “Durvalumab and tremelimumab significantly prolonged overall survival in patients with refractory colorectal carcinoma and preserved quality of life. Adverse events were more frequent with durvalumab and tremelimumab. This is the first study showing that combined PD-L1 and CTLA-4 inhibition prolongs survival in patients with advanced refractory colorectal carcinoma not selected for defective mismatch repair.”
Disclosure: The study authors' full disclosures can be found at coi.asco.org.
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