Durvalumab Plus Chemotherapy Improves Outcomes in Biliary Tract Cancer Across Primary Tumor Locations

Ruth He, MD, Lombardi Comprehensive Cancer Center at Georgetown University, Washington, DC, reviews the findings from a subgroup analysis of the phase 3 TOPAZ-1 study which evaluated the outcomes by primary tumor location in patients with advanced biliary tract cancer (intrahepatic or extrahepatic cholangiocarcinoma, or gallbladder cancer) who received gemcitabine and cisplatin chemotherapy, plus either durvalumab or placebo, in the first line setting.

These findings were presented at the 2022 ESMO World Congress on Gastrointestinal Cancer in Barcelona, Spain.

Transcript:

Hi, I'm Doctor Ruth He from Lombardi Comprehensive Cancer Center, Washington DC in the United States. I have presented an oral abstract on the results of a subgroup analysis by primary tumor locations of the phase 3 TOPAZ-1 study, at ESMO GI in Barcelona, Spain. As you know, the primary results of the TOPAZ-1 study were presented at this year's ASCO meeting.

TOPAZ-1 is a randomized double blind, multicenter global phase 3 study. Patients with local advanced or metastatic biliary tract cancer were randomized 1:1 to durvalumab plus gemcitabine and cisplatin (GemCis), or placebo plus GemCis for 8 cycles followed by the durvalumab or placebo monotherapy until disease progression or unacceptable toxicities. The randomization was stratified by disease status, initially unresectable versus recurrent, and primary tumor locations: intrahepatic cholangiocarcinoma versus extrahepatic cholangiocarcinoma versus gallbladder cancer.

The study met its primary end point, which was overall survival. As previously mentioned, a statistically significant improvement in overall survival was observed with a hazard ratio for the durvalumab versus placebo of 0.80. There is often a delayed separation of immunotherapy plus chemotherapy versus chemotherapy alone. To explore this further, a piece-wise hazard ratio was calculated. The hazard ratio for the durvalumab versus placebo from 0 to 6 months was 0.91, and after 6 months was 0.74, demonstrating the long-term survival benefit with the durvalumab plus gemcitabine. Since cholangiocarcinoma is very heterogeneous, the benefit of adding durvalumab to GemCis was studied across primary tumor types: intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, and gallbladder cancer. The benefit was also explored based on the geographic area of patients enrolled in the study: Asia, Europe, North America, and South America.

In addition, to evaluate the efficacy of the durvalumab plus GemCis in the Western population, the hazard ratio from patients enrolled in Europe and North America was calculated. Certain tumor primary locations in certain geographic areas were not calculated because of an insufficient number of events. The conclusion from this analysis shows the benefit of the durvalumab plus GemCis was seen in intrahepatic cholangiocarcinoma, and extrahepatic cholangiocarcinoma.

Gallbladder cancer has a unique geographic distribution based on epidemiology studies and has shown a higher hazard ratio in the subgroup analysis. An additional study was carried out on gallbladder cancer. Interestingly, the hazard ratio calculated on gallbladder cancer in Asia, Europe, and North American plus South America all favor durvalumab versus placebo. The sample size from South America was very small; however, this group of patients who received the placebo plus chemotherapy outperformed the expectation of other primary tumor locations.

In addition, secondary study end points were evaluated in this exploratory subgroup analysis. Progression free survival, overall response rate, and proportion of patients with durable response were improved across primary tumor locations. As far as the primary study end point of overall survival, a benefit was observed across primary tumor locations. Safety finding were generally consistent across primary tumor locations. In conclusion, in this subgroup analysis of the TOPAZ-1 study by primary tumor locations, the addition of the durvalumab to GemCis improved clinical benefit in patients with advanced biliary tract cancer. Thank you.

Source:

He A, Valle J, Lee C, et al. Outcomes by primary tumour location in patients with advanced biliary tract cancer treated with durvalumab or placebo plus gemcitabine and cisplatin in the Phase 3 TOPAZ-1 study. Presented at: ESMO World Congress on Gastrointestinal Cancer; June 29-July 2, 2022. Barcelona, Spain. Abstract O-1.