Durvalumab + gemcitabine-cisplatin benefit in biliary tract cancer consistent across tumour locations

The benefit of adding durvalumab to gemcitabine plus cisplatin chemotherapy in patients with advanced biliary tract cancer (BTC) was consistent regardless of primary tumour location, according to a subgroup analysis of the phase III TOPAZ-1 study presented at ESMO GI 2022.

The 685 patients in this multinational study had previously untreated unresectable or metastatic BTC* or disease recurrence >6 months following curative surgery or adjuvant therapy, and an ECOG performance status of 0–1. A majority of the patients had intrahepatic cholangiocarcinoma (n=383), while 131 and 171 had extrahepatic cholangiocarcinoma and gallbladder cancer, respectively. They were randomized 1:1 to receive durvalumab (1,500 mg) or placebo Q3W plus up to eight cycles of gemcitabine (1,000 mg/m²) plus cisplatin (25 mg/m²). This was followed by durvalumab 1,500 mg Q4W or placebo in the respective groups until disease progression.

Previously published results showed an improvement in overall survival (OS) and progression-free survival (PFS) with durvalumab vs placebo (OS: median 12.8 vs 11.5 months; hazard ratio [HR], 0.80, 95 percent confidence interval [CI], 0.66–0.97; p=0.021; PFS: median 7.2 vs 5.7 months; HR, 0.75, 95 percent CI, 0.63–0.89; p=0.001). [NEJM Evid 2022;doi:10.1056/EVIDoa2200015]

The present analysis demonstrated that the improvement in OS with durvalumab vs placebo was consistent regardless of primary tumour location (intrahepatic cholangiocarcinoma: median 13.5 vs 11.5 months; HR, 0.76, 95 percent CI, 0.58–0.98; extrahepatic cholangiocarcinoma: median 12.7 vs 12.1 months; HR, 0.76, 95 percent CI, 0.49–1.19; gallbladder cancer: median 10.7 vs 11.0 months; HR, 0.94, 95 percent CI, 0.65–1.37). [ESMO GI 2022, abstract O-1]

The PFS benefit with durvalumab vs placebo was also consistent regardless of primary tumour location (intrahepatic cholangiocarcinoma: median 7.3 vs 6.0 months; HR, 0.79, 95 percent CI, 0.64–0.99; extrahepatic cholangiocarcinoma: median 7.6 vs 5.7 months; HR, 0.52, 95 percent CI, 0.35–0.78; gallbladder cancer: median 6.1 vs 5.6 months; HR, 0.90, 95 percent CI, 0.65–1.24).

Objective response rate (ORR) was 26.7 and 18.7 percent in the durvalumab and placebo groups, respectively, in the overall population (odds ratio [OR], 1.60). ORR was 24.7 and 15.5 percent, respectively, among those with intrahepatic cholangiocarcinoma (OR, 1.79), 28.8 and 15.6 percent, respectively, in those with extrahepatic cholangiocarcinoma (OR, 2.18), and 29.4 and 27.9 percent, respectively, in those with gallbladder cancer (OR, 1.08).

Time to response was shorter in the durvalumab vs placebo group in the overall population (median 1.6 vs 2.7 months) as well as in those with extrahepatic cholangiocarcinoma (median 1.4 vs 2.6 months) and gallbladder cancer (median 1.4 vs 2.7 months), and comparable between groups in those with intrahepatic cholangiocarcinoma (median 2.8 vs 2.7 months). Duration of response was 6.4 vs 6.2 months in the overall population, 6.0 months for both groups in those with intrahepatic carcinoma, 8.9 vs 6.2 months in those with extrahepatic cholangiocarcinoma, and 6.0 vs 6.6 months in those with gallbladder cancer.

Grade 3–4 treatment-related adverse events (TRAEs) occurred in 57.4 and 58.5 percent of durvalumab and placebo recipients, respectively, with intrahepatic cholangiocarcinoma, 60.6 and 75.0 percent, respectively, with extrahepatic cholangiocarcinoma, and 69.0 and 65.9 percent, respectively, with gallbladder cancer. TRAEs led to discontinuation in 8.5 and 14.0 percent, respectively, with intrahepatic cholangiocarcinoma, 12.1 and 3.1 percent, respectively, with extrahepatic cholangiocarcinoma, and 7.1 and 11.8 percent, respectively, with gallbladder cancer. TRAEs led to death in one durvalumab recipient with intrahepatic cholangiocarcinoma, one durvalumab recipient with extrahepatic cholangiocarcinoma, and one placebo recipient with gallbladder cancer.

“In this subgroup analysis of the TOPAZ-1 study … addition of durvalumab to gemcitabine-cisplatin was associated with improved clinical benefit in patients with advanced BTC [with] OS benefit observed across primary tumour locations,” said study author Associate Professor Aiwu Ruth He from the Georgetown Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, US. In addition, PFS and ORR were also improved with durvalumab regardless of tumour location, while safety outcomes were consistent, she said.

“These findings support durvalumab plus gemcitabine-cisplatin as a first-line treatment option for advanced BTC, irrespective of primary tumour location,” He concluded.