Regional Subgroup Analysis of Durvalumab plus GemCis in Advanced BTCs: The TOPAZ-1 Study

September 2022, Vol 3, No 3 — September 29, 2022

The randomized, double-blind, global, phase 3 TOPAZ-1 trial demonstrated that the first-line PD-L1 inhibitor durvalumab plus gemcitabine/cisplatin (GemCis; median follow-up, 16.8 months) as first-line treatment significantly improved overall survival (OS) versus placebo plus GemCis (median follow-up, 15.9 months) in patients with advanced biliary tract cancers (BTCs).1 At the 2022 ASCO annual meeting, data were presented from a prespecified subgroup analysis that assessed efficacy outcomes for patients enrolled in Asia and the rest of the world (RoW).

In the trial, 685 eligible patients were randomly assigned 1:1 to receive durvalumab (n = 341; 1500 mg once every 3 weeks [Q3W]) or placebo (n = 344) in combination with GemCis (gemcitabine 1000 mg/m2; cisplatin 25 mg/m2, days 1 and 8, Q3W) for up to 8 cycles, followed by durvalumab (1500 mg every 4 weeks) or placebo monotherapy until disease progression or unacceptable toxicity. The prespecified subgroup analysis assessed 2 cohorts: those enrolled in Asia (China, Hong Kong, India, Japan, South Korea, Taiwan, Thailand) or RoW (Europe [Bulgaria, France, Italy, Poland, Russia, Turkey, United Kingdom], North America [United States], and South America [Argentina, Chile]).

A total of 374 patients were included in the Asia cohort (54.6%), and 311 (45.4%) patients were in the RoW cohort. Some differences in baseline characteristics were seen between the 2 regional groups for durvalumab-treated patients, including recurrent disease (Asia, 23%; RoW, 14.5%), ECOG performance status 1 (Asia, 59.1%; RoW, 41.2%), and metastatic disease (Asia, 89.3%; RoW, 82.0%). In addition, in the placebo arm, a higher proportion of patients in Asia received subsequent anticancer therapies than in the RoW group (53.6% vs 43.9%). Median duration of follow-up in censored patients was longer in Asia versus the RoW in both groups (durvalumab, 14.8 months vs 13.0 months; placebo, 13.8 months vs 12.1 months).

Overall, regional-level analysis showed that outcomes were generally similar and approximated the overall populations for Asia, Europe, and North America, with OS showing a trend in favor of durvalumab compared with placebo across most regions except South America, where placebo performed better. It is notable that OS was significantly better with the addition of durvalumab to GemCis in Asia, suggesting that the impact on OS of durvalumab in Asia was greater than what was seen in the RoW cohort. Despite a higher prevalence of hepatitis B infection in patients enrolled in Asia, survival outcomes were similar in patients with and without viral hepatitis.

The safety profile of durvalumab plus GemCis was similar between the 2 regional groups and was generally manageable. Grade 3/4 adverse events were predominantly hematologic for both arms and regions and similar for Asia (durvalumab, 78.5%; placebo, 78.6%) and RoW (durvalumab, 72.7%; placebo, 76.7%).

According to the researchers, results of the subgroup analyses showed that “despite some regional differences in baseline prognostic characteristics, OS trends favored durvalumab compared with placebo in both Asia and RoW, supporting the use of durvalumab plus GemCis as a potential new first-line treatment option for all patients with BTCs.”


  1. Oh D-Y, He AR, Qin S, et al. Durvalumab plus gemcitabine and cisplatin in advanced biliary tract cancer. NEJM Evid. 2022;1(8). Published online June 1, 2022.

Source: Vogel A, Chen L-T, He AR, et al. Regional subgroup analysis of the phase 3 TOPAZ-1 study of durvalumab plus gemcitabine and cisplatin in advanced biliary tract cancer (BTC). Abstract 4075.

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