FDA approved Imfinzi plus chemotherapy as a first-line treatment regimen for advanced biliary tract cancer

Biliary tract cancer (BTC) is a form of gastrointestinal cancer that occurs in the bile duct, gallbladder, and ampulla of Vater (an area where the bile duct and pancreas join to open to the small intestine). Most cases of BTC are diagnosed at an advanced stage due to a lack of early detection tools and by when the treatment options are limited. The current treatment guideline for BTC is chemotherapy (gemcitabine and cisplatin), with a median overall survival of 11.7 months post-diagnosis. This warrants the need for new therapies for treating BTC.

Imfinzi (durvalumab) is the new hope for patients with BTC. When administered with chemotherapy, the risk of death is reduced by 20% compared to chemotherapy alone. A quarter of patients will survive for two years compared to the placebo, where the estimate is only one-tenth. Programmed cell death ligand-1 (PDL-1), a member of the B7/CD28 family of proteins, is expressed in BTC. It functions by inhibiting the T cell activation leading to a reduced antitumor T-cell response. Imfinzi is a human monoclonal antibody that binds to PDL-1, enabling the natural immune responses to take over and work against the tumor.

TOPAZ-1 (NCT03875235) is a randomized, double-blind, placebo-controlled, multicentre (105 centers across 17 countries), global Phase III trial of a) Imfinzi in combination with chemotherapy (gemcitabine plus cisplatin) b) Placebo in combination with chemotherapy targeting patients with unresectable advanced or metastatic BTC. The baseline characteristics were generally well balanced between the treatment groups, and the investigators randomized the patients by disease status and primary tumor location. The key exclusion criteria were patients who previously had ampullary carcinoma.

Patients in the Imfinzi arm had significantly longer overall survival – the primary endpoint – with close to 25% compared to less than 11% in the placebo arm (hazard ratio [HR] 0.80; 95% confidence interval [CI] 0.66-0.97; p=0.021). Patients with BTC had acceptable tolerance with Imfinzi plus chemotherapy, and adverse events were similar in the two groups. TOPAZ-1 Phase III trial results are published in the New England Journal of Medicine Evidence.

Imfinzi plus chemotherapy is listed in the NCCN clinical practice guidelines in Oncology as first-line therapy for locally advanced or metastatic BTC. Imfinzi is also approved for treating: extensive-stage small cell lung cancer; unresectable, stage III non-small cell lung cancer (second line of treatment); and advanced bladder cancer.

AstraZeneca developed Imfinzi, and currently, a clinical program is underway to use Imfinzi as a single treatment or in combination with novel antibodies to treat multiple tumor types.