In a post hoc analysis of the global phase III TOPAZ-1 trial published in JAMA Oncology, Oh et al found that the addition of durvalumab to chemotherapy with gemcitabine and cisplatin was associated with long-term survival benefit and a clinically manageable safety profile in patients with previously untreated advanced biliary tract cancer.
“Durvalumab plus gemcitabine and cisplatin was recently established as the first-line standard of care among patients with advanced biliary tract cancer” based on the primary TOPAZ-1 analysis, which demonstrated significantly improved overall survival with comparable safety vs placebo plus gemcitabine and cisplatin, the investigators commented. After more than 4 years of follow-up, “these findings continue to support [this regimen] as a first-line treatment option….”
Study Details
Between April 2019 and December 2020, TOPAZ-1 enrolled adult patients with histologically confirmed unresectable, locally advanced, or metastatic biliary tract adenocarcinoma at 105 sites across 17 countries.
A total of 685 patients (median age = 64 years) were randomly assigned in a 1:1 ratio to receive gemcitabine (1,000 mg/m2) and cisplatin (25 mg/m2) plus either durvalumab (1,500 mg) or placebo on days 1 and 8 every 3 weeks for up to eight cycles, followed by durvalumab or placebo monotherapy every 4 weeks.
In this post hoc analysis, follow-up data for censored patients were provided for a median of 56.9 and 50.7 months, respectively. Overall survival, treatment exposure duration, serious adverse events, and adverse events leading to treatment discontinuation were assessed at approximately 48 months after randomization of the last patient.
Key Findings
Median overall survival was 13.0 months with durvalumab plus gemcitabine and cisplatin vs 11.4 months with placebo plus gemcitabine and cisplatin (hazard ratio = 0.75, 95% confidence interval = 0.64–0.88), with corresponding 48-month rates of 11.8% and 4.3%.
Serious adverse events considered possibly related to treatment were found to occur at similar rates in the durvalumab (15.4%) and placebo (17.3%) arms. A total of 6.2% and 5.3% of patients, respectively, experienced adverse events leading to treatment discontinuation.
“To our knowledge, the phase III TOPAZ-1 randomized clinical trial is the first to report 4-year overall survival among participants with advanced biliary tract cancer treated with immunotherapy plus chemotherapy,” the investigators concluded. “The final post hoc findings of this trial demonstrate the long-term sustained benefit and clinically manageable safety profile of durvalumab plus gemcitabine and cisplatin for participants with advanced biliary tract cancer, supporting the regimen as a standard-of-care treatment in these participants.”
Do-Youn Oh, MD, PhD, of Seoul National University Hospital, Korea, is the corresponding author of the article in JAMA Oncology.
Disclosure: The study was sponsored by AstraZeneca. For full disclosures of the study authors, visit jamanetwork.com.
