Patients With Biliary Tract Cancers Benefit From Durvalumab Plus Chemotherapy


Checkpoint inhibitors may have clinical utility in BTC based on immunogenic features of the disease; however, limited clinical activity has been observed with single-agent therapy in the advanced setting.

Do-Youn Oh, MD, PhD

Do-Youn Oh, MD, PhD

The PD-L1 inhibitor durvalumab (Imfinzi) in conjunction with gemcitabine and cisplatin demonstrated superior overall survival (OS) in patients with advanced biliary tract cancer (BCT) compared with placebo, according to the results of the phase 3 TOPAZ-1 trial (NCT03875235) that will be presented during the 2022 Gastrointestinal Cancers Symposium.1,2

The findings demonstrated a 20% reduction in the risk of death with durvalumab plus chemotherapy vs placebo plus chemotherapy in this patient population (HR, 0.80; 95% CI, 0.66-0.97; P =.021).

At a median follow-up of 13.7 months in the durvalumab/chemotherapy arm and 12.6 months in the placebo/chemotherapy arm, the median OS was 12.8 months (95% CI, 11.1-14) vs 11.5 months (95% CI, 10.1-12.5), respectively. The 18-month OS rates were 35.1% (95% CI, 29.1%-41.2%) vs 25.6% (95% CI, 19.9%-31.7%), respectively. The 24-month OS rates were 24.9% (95% CI, 17.9%-32.5%) vs 10.4% (95% CI, 4.7%-18.8%), respectively.

“TOPAZ-1 is the first phase 3 trial to show that adding immunotherapy to standard chemotherapy can increase survival in [BTC], and importantly, does so without inducing any new serious [adverse] effects [AEs],” lead study author Do-Youn Oh, MD, PhD, a professor in the Division of Medical Oncology of the Department of Internal Medicine at Seoul National University Hospital and Seoul National University College of Medicine in Seoul, South Korea, said in a news release.2

BTC is a rare and heterogenous type of cancer that is associated with poor patient outcomes. Checkpoint inhibitors may have clinical utility in BTC based on immunogenic features of the disease; however, limited clinical activity has been observed with single-agent therapy in the advanced setting.

Gemcitabine plus cisplatin has been the standard chemotherapy option for patients with advanced BTC in the United States.

“The current standard of care for inoperable biliary tract cancer is combined chemotherapy. That standard has not changed in over a decade. TOPAZ-1 is the first phase 3 trial to demonstrate the benefit of immunotherapy for improved [OS], in combination with chemotherapy, creating a new standard of care. Patients have a greater reason for hope given the positive results seen with the use of immunotherapy in [BTC],” said Cathy Eng, MD, FACP, FASCO, the David H. Johnson Chair in Surgical and Medical Oncology at Vanderbilt-Ingram Cancer Center.

Moreover, the results of a phase 2 study demonstrated encouraging antitumor activity with durvalumab in combination with gemcitabine and cisplatin for patients with advanced BTC. As such, the TOPAZ-1 trial was developed to further evaluate the immunotherapy-containing regimen compared with chemotherapy alone.

The double-blind study randomized 685 patients with previously untreated, unresectable locally advanced, recurrent, or metastatic BTC 1:1 to receive 1500 mg of durvalumab every 3 weeks vs placebo plus 1000 mg/m2 of gemcitabine and 25 mg/m2 of cisplatin on days 1 and 8 every 3 weeks. Patients were treated for up 8 cycles, which was followed by 1500 mg of durvalumab every 4 weeks or placebo until disease progression or unacceptable toxicity.

Patients were stratified by disease status (initially unresectable vs recurrent) and primary tumor location (intrahepatic cholangiocarcinoma vs extrahepatic cholangiocarcinoma vs gallbladder cancer).

The primary end point of the study was OS; secondary end points included progression-free survival (PFS), objective response rate (ORR), and safety.

Overall, 341 patients were randomized to durvalumab/chemotherapy and 344 were randomized to placebo/chemotherapy. The median age was 64 years in both arms and approximately half of patients were female (50.4% vs 48.8%, respectively) with an ECOG performance status of 0 (50.7% vs 47.4%, respectively).

Notably, 55% of patients had intrahepatic cancers, 19% had extrahepatic cancers, and 25% had gallbladder cancer.

Patients were enrolled from centers in the United States, as well as 17 other countries; over half of patients (55%) were enrolled from centers in Asian countries, including South Korea, Thailand, Japan, and China.

Further results showed that the median PFS was 7.2 months (95% CI, 6.7-7.4) with durvalumab plus gemcitabine and cisplatin vs 5.7 months (95% CI, 5.6-6.7) with placebo plus gemcitabine and cisplatin (HR, 0.75; 95% CI, 0.64-0.89; P = .001).

The ORR was 26.7% with durvalumab compared with 18.7% with placebo.

Regarding safety, the most common AEs included anemia (48.2%), neutropenia (31.7%), and nausea (40.2%). Potentially serious AEs were observed in 62.7% of patients receiving the durvalumab-containing regimen compared with 64.9% of patients receiving the placebo-containing regimen. Notably, this suggests that most AEs resulted from the chemotherapeutic agents.

Additionally, grade 3 or 4 AEs were observed in 75.7% of patients who received durvalumab/gemcitabine/cisplatin (n = 338) compared with 77.8% of patients who received placebo/gemcitabine/cisplatin (n = 342). Treatment-related AEs (TRAEs) leading to discontinuation of any drug were observed in 8.9% vs 11.4% of patients, respectively. TRAEs leading to death occurred in 0.6% vs 0.3% of patients, respectively.

“We are hopeful that durvalumab plus gemcitabine and cisplatin will become a new standard of care for advanced [BTC]. Our first task at this time is boosting communication with patients and family members about the potential for this immunotherapy combination and what it may mean for their ongoing care,” concluded Oh.


  1. Oh DY, He AR, Qin S, et al. A phase 3 randomized, double-blind, placebo-controlled study of durvalumab in combination with gemcitabine plus cisplatin (GemCis) in patients (pts) with advanced biliary tract cancer (BTC): TOPAZ-1. J Clin Oncol. 2022;40(suppl; abstr 378).
  2. Durvalumab significantly improves survival for patients with biliary tract cancer compared to chemotherapy alone. News release. ASCO. January 18, 2022. Accessed January 18, 2022.
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