Posted: Friday, September 30, 2022
In the global phase III TOPAZ-1 trial, first-line treatment with the PD-L1 inhibitor durvalumab plus chemotherapy significantly improved overall survival compared with the placebo plus chemotherapy in patients with advanced biliary tract cancer, according to Juan W. Valle, MD, of The University of Manchester and the Christie National Health Service Foundation Trust, United Kingdom, and colleagues. The results of the preplanned interim analysis, which were published in NEJM Evidence, revealed similar safety profiles between the arms.
“Biliary tract cancer exhibits immunogenic features, including expression of the immune checkpoint molecules PD-L1 and CTLA-4, in the tumor microenvironment,” the investigators commented. “A phase II trial of durvalumab in combination with gemcitabine and cisplatin demonstrated promising efficacy…in a nonrandomized, single-center study, establishing proof of concept for this approach in advanced biliary tract cancer.”
Patients with previously untreated unresectable or metastatic biliary tract cancer, as well as those who developed recurrent disease, were randomly assigned in a 1:1 ratio to receive durvalumab (n = 341) or a placebo (n = 344) in combination with a standard-of-care chemotherapy regimen consisting of gemcitabine plus cisplatin for up to eight cycles; this was followed by monotherapy with durvalumab or the placebo until disease progression or unacceptable toxicity.
A total of 58.1% of the durvalumab arm and 65.7% of the placebo arm had died as of data cutoff. The hazard ratio for overall survival was 0.80 (P = .021). The estimated 24-month overall survival rate was higher with durvalumab than with the placebo (24.9% vs. 10.4%). The hazard ratio for progression-free survival was 0.75 (P = .001). The objective response rates were 26.7% and 18.7% with durvalumab and the placebo, respectively. The rate of grade 3 or 4 adverse events was 75.7% with durvalumab and 77.8% with the placebo.
Disclosure: For full disclosures of the study authors, visit evidence.nejm.org.