From the Journals

Potential new standard of care for biliary tract cancer



Adding the checkpoint inhibitor durvalumab (Imfinzi) to chemotherapy significantly improved overall survival in patients with advanced biliary tract cancer, as compared to chemotherapy alone, according to interim results from the TOPAZ-1 trial.

The risk of death for those taking durvalumab plus chemotherapy was 20% lower than for patients on chemotherapy alone. At 18 months, overall survival was 35.1% in the durvalumab group versus 25.6% for chemotherapy alone. By 2 years, overall survival was 24.9% versus 10.4%.

“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 lead author Do-Youn Oh, MD, PhD, professor in the Division of Medical Oncology at Seoul National University Hospital and Seoul National University College of Medicine, Korea.

“The study met its primary endpoint at a prespecified interim analysis, and durvalumab plus gemcitabine and cisplatin demonstrated statistically significant and clinically meaningful prolonged overall survival compared with placebo plus chemotherapy,” she said.

“This is an effective first-line therapy and could become a new standard of care for patients with advanced biliary tract cancer,” she added.

Dr. Oh presented the results at the Gastrointestinal Cancers Symposium (GICS) 2022.

In a discussion of the paper, Nilofer Saba Azad, MD, from the department of oncology, Johns Hopkins Sidney Kimmel Cancer Center, Baltimore, noted that overall, “we are seeing enticing benefit in survival and response rate.”

“There is moderately strong preliminary clinical data and biological rationale that immune checkpoint may have some activity in biliary tract cancer,” she said. “The trial was adequately powered and accounted for important known clinical subsets, and [it] was placebo controlled. The results suggest a meaningful benefit for patients.”

However, she pointed out that there are still open questions, mostly having to do with the subgroup analysis.

Biliary tract cancer: Incidence is rising

Biliary tract cancers are a relatively rare and heterogeneous group of cancers, and global incidence is rising. “Advanced unresectable biliary tract cancer is an area of high unmet need due to its aggressive nature, limited treatment options, and poor prognosis,” explained Dr. Oh. “The first-line standard of care for advanced biliary tract cancers, gemcitabine and cisplatin, has remained unchanged for over a decade.”

Previous research has suggested that checkpoint inhibition may result in antitumor immune responses, she commented. A previous phase 2 trial showed that durvalumab combined with gemcitabine and cisplatin showed promising antitumor activity in advanced biliary tract cancer. This latest study is a larger phase 3 trial to investigate this effect further.

The study involved 365 patients with unresectable locally advanced, recurrent, or metastatic biliary tract cancers. Patients had one of three types of biliary tract cancer: 55% had intrahepatic cancers; 19% had extrahepatic cancers; and 25% had gallbladder cancer.

The trial was conducted in the U.S. and 17 countries in Europe, South America, and Asia. Nearly 55% of the cohort was from Asia, including South Korea, Thailand, Japan, and China.

All patients received chemotherapy with gemcitabine (1,000 mg/m2) and cisplatin (25 mg/m2 on days 1 and 8 every 3 weeks) for up to eight cycles.

Patients were randomized to receive either durvalumab (1,500 mg every 3 weeks) or placebo before chemotherapy and also to receive durvalumab (1,500 mg every 4 weeks) or placebo after chemotherapy until disease progression or unacceptable toxicity.

At approximately 1 year, the authors found that adding durvalumab significantly improved overall survival (hazard ratio, 0.80; P = .021).

Progression-free survival was also significantly better with durvalumab compared to placebo: 7.2 months versus 5.7 months (HR, 0.75; P = .001).

The overall response rate (ORR) was 26.7% with durvalumab and 18.7% with placebo.

The most common adverse events were anemia (experienced by 48.2% of patients), neutropenia (31.7%), and nausea (40.2%). Grade 3/4 adverse events occurred in 75.7% of patients receiving durvalumab versus 77.8% for placebo, indicating that the majority of side effects in both arms were from chemotherapy, Dr. Oh commented. Discontinuation of any study medication because of toxicity occurred in 8.9% and 11.4% of patients, respectively.


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