Addition of durvalumab to chemotherapy prolongs survival in advanced biliary tract cancer
The addition of durvalumab to gemcitabine and cisplatin significantly extended OS among patients with advanced biliary tract cancer, according to results of a phase 3 study scheduled for presentation at ASCO Gastrointestinal Cancers Symposium.
The findings of the randomized TOPAZ-1 trial suggested the combination of the PD-L1 checkpoint inhibitor durvalumab (Imfinzi, AstraZeneca) and chemotherapy may be a new standard of care for first-line treatment of this patient population, researchers wrote.
“This is the first global phase 3 study to compete with gemcitabine and cisplatin,” Do-Youn Oh, MD, PhD, professor in the division of medical oncology in the department of internal medicine at Seoul National University Hospital and Seoul National University College of Medicine, told Healio. “The TOPAZ-1 population represents the real-world biliary tract cancer situation. All physicians, investigators and patients/family members have been waiting for this kind of success in this biliary tract cancer field.”
Background and methodology
Oh and colleagues pursued the research because immunogenic features of biliary tract cancer suggested checkpoint inhibition may result in antitumor immune responses, and single agents have shown limited clinical activity in advanced settings. Additionally, durvalumab demonstrated promising antitumor activity in a phase 2 study.
“The first-line current standard of care for biliary tract cancer (gemcitabine and cisplatin) has remained unchanged for over a decade,” Oh said. “In our previous experiences with immune checkpoint inhibitors, the monotherapy has shown modest efficacy, in general, in biliary tract cancer.”
The international, double-blind trial included 685 patients previously untreated for unresectable locally advanced, recurrent or metastatic biliary tract cancer.
Researchers randomly assigned the patients 1:1 to gemcitabine and cisplatin with either 1,500 mg durvalumab every 3 weeks (n = 341; median age, 64 years; range, 20-84; 50.4% women) or placebo (n = 344; median age, 64 years; range, 31-85; 48.8% women). Patients received 1,000 mg/m2 and 25 mg/m2 cisplatin on days 1 and 8 every 3 weeks for up to eight cycles, after which they continued to receive 1,500 mg durvalumab every 4 weeks or placebo until disease progression or unacceptable toxicity.
OS served as the primary objective; secondary endpoints included PFS, objective response rate and safety.
Key findings
Results showed durvalumab plus chemotherapy significantly improved OS (median, 12.8 months vs. 11.5 months; HR = 0.8; 95% CI, 0.66–0.97) and PFS (median, 7.2 months vs. 5.7 months; HR = 0.75; 95% CI, 0.64–0.89) compared with placebo and chemotherapy.
After a year and a half on the trial, 35.1% of patients on durvalumab remained alive compared with 25.6% on placebo. The durvalumab group also had a higher rate of 2-year OS (24.9% vs. 10.4%) and a higher ORR (26.7% vs. 18.7%), and lower rates of grade 3 to grade 4 treatment-related adverse events (62.7% vs. 64.9%) and adverse events that led to discontinuation of any study medication (8.9% vs. 11.4%).
Implications
The study showed immunotherapy can increase survival without inducing any new serious adverse events, Oh said.
In further research, Oh and colleagues will investigate diverse immunotherapy agents in biliary tract cancer, as well as biomarkers for such treatments.
“Immunotherapy is working in biliary tract cancer. This study is the first step to boost research and new drug development with immunotherapy in biliary tract cancer,” Oh told Healio.
References:
Durvalumab significantly improves survival for patients with biliary tract cancer compared to chemotherapy alone. https://www.asco.org/about-asco/press-center/news-releases/durvalumab-significantly-improves-survival-patients-biliary. Published Jan. 18, 2022. Accessed Jan. 18, 2022.
Oh D-Y, et al. Abstract 378. Presented at: Gastrointestinal Cancers Symposium; Jan. 20-22, 2022; San Francisco.
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Oh D-Y, et al. Abstract 378. Presented at: Gastrointestinal Cancers Symposium Jan. 20-22, 2022; San Francisco.