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TOPAZ-1: Phase 3 Study Finds Durvalumab in Biliary Tract Cancer Significantly Improves OS, PFS Compared With Chemo Alone


There has not been a change in the standard of care in this type of cancer in a decade, according to an expert from ASCO.

Pairing durvalumab (Imfinzi) with the chemotherapy combination gemcitabine and cisplatin improved overall survival (OS) by 20% in patients with advanced biliary tract cancer, compared with the current standard of giving the chemotherapy combination alone, according to phase 3 trial results released today.

Findings from TOPAZ-1 will be presented at the American Society of Clinical Oncology Gastrointestinal Cancers Symposium (ASCO GI), set for January 20-22 in San Francisco, California.

Data show that after 18 months on the study, 35.1% of those taking durvalumab with the chemotherapy combination were still alive, compared with 25.6% taking just the chemotherapy. At 24 months, the difference was 24.9% and 10.4%.

The 3 therapies work in concert to attack cancer cells and promote their demise. The immune checkpoint inhibitor durvalumab blocks the PD-L1 protein on the surface of immune cells, which lets the immune system to recognize and attack cancer cells. Meanwhile, gemcitabine promotes the death of cancer cells that are rapidly dividing, while cisplatin blocks the DNA repair mechanisms in cancer cells, leading to their death.

“TOPAZ-1 is the first phase 3 trial to show that adding immunotherapy to standard chemotherapy can increase survival in biliary tract cancer, and importantly, does so without inducing any new serious side effects,” said principal investigator Do-Youn Oh, MD, PhD, professor in the Division of Medical Oncology, Department of Internal Medicine at Seoul National University Hospital and Seoul National University College of Medicine, said in a statement.

Biliary tract cancers are relatively rare, and diagnosis often occurs when the disease has already advanced, which often makes for a grim prognosis. There have been few treatment advances in this area, which makes the results of TOPAZ-1 encouraging, according to experts in the field.

“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 overall survival, in combination with chemotherapy, creating a new standard of care,” Cathy Eng, MD, FACP, said in a statement released by ASCO. “Patients have a greater reason for hope given the positive results seen with the use of immunotherapy in biliary tract cancers.”

There were fewer than 12,000 new cases of gallbladder cancer diagnosed in the United States in 2021, with 4310 deaths.

In TOPAZ-1, 685 patients with inoperable, locally advanced, recurrent, or metastatic biliary tract cancer were randomly assigned to receive durvalumab or a placebo. Patients, who had not been previously treated, also received the current standard of care for the disease, gemcitabine plus cisplatin.

Among those in the study, 55% had intrahepatic cancers, occurring in bile ducts inside the liver; 19 % had extrahepatic cancers, which form outside the liver; and 25% had gallbladder cancer. The international trial was conducted in the United States and 17 other countries.

Patients received 1500 mg of durvalumab every 3 weeks with 1000 mg/m2 of gemcitabine and and 25 mg/m2 of cisplatin on days 1 and 8 and then every 3 weeks up to 8 cycles, followed by durvalumab 1500 mg every 4 cycles or placebo until disease progression or unacceptable toxicity. Primary end point was OS; secondary end points were progression-free survival (PFS), objective response rate (ORR) and safety. Results showed the following:

  • At data cutoff for the interim analysis August 11, 2021, the durvalumab group had improved OS with a hazard ratio (HR) of 0.80 (95% CI, 0.66-0.97; P = .021).
  • PFS was significantly improved for the durvalumab group (HR 0.75; 95% CI, 0.64-0.89; P = .001).
  • ORR was 26.7% for durvalumab and 18.7% for placebo.
  • Grade 3 or 4 treatment-related adverse events were seen in 62.7% of durvalumab patients and 64.9% of those taking placebo. Treatment-related AEs led to discontinuation of medication for 8.9% of patients in the durvalumab group and 11.4% in the placebo group.

Oh said he hoped that this new combination of durvalumab plus chemotherapy would become the new standard of care in biliary tract cancer. “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,” he said in a statement released by ASCO.

AstraZeneca funded the study.


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. Presented at: American Society of Clinical Oncology Gastrointestinal Cancers Symposium (ASCO GI), January 20-22, 2022; San Francisco, CA; Abstract 378.

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