Durvalumab plus chemo delivers sustained survival benefits in advanced BTC

A 3-year update from the phase III TOPAZ-1 study has shown sustained survival benefit and manageable safety with durvalumab plus gemcitabine and cisplatin (GemCis) relative to placebo among patients with advanced biliary tract cancer (BTC).

“These updated exploratory analyses further support the use of durvalumab plus GemCis as standard-of-care treatment for people with locally advanced or metastatic BTC,” the investigators said.

A total of 685 patients with advanced BTC were randomly allocated to receive either durvalumab plus GemCis (n=341) or placebo plus GemCis (n=344) every 3 weeks (≤8 cycles). Participants then received durvalumab or placebo monotherapy every 4 weeks until disease progression or other discontinuation criteria were met.

The investigators assessed overall survival (OS) and serious adverse events in the full analysis and safety analysis sets, respectively. They also evaluated the extended long-term survivor (eLTS) outcomes among the full analysis set participants alive ≥30 months after randomization.

Over a median follow-up of 41.3 months, the median OS was 12.9 months (95 percent confidence interval [CI], 11.6‒14.1) for durvalumab plus GemCis and 11.3 months (95 percent CI, 10.1‒12.5) for placebo plus GemCis (hazard ratio, 0.74, 95 percent CI, 0.63‒0.87). [J Hepatol 2025;83:1092-1101]

The OS rate at 36 months was 14.6 percent vs 6.9 percent, respectively. In 566 patients (82.6 percent) who achieved disease control, the 36-month OS rate was significantly higher with durvalumab plus GemCis than with placebo plus GemCis (17.0 percent vs 7.6 percent).

Of the patients, 12.8 percent were eLTS, with the durvalumab group having more survivors (17.0 percent vs 8.7 percent). Moreover, durvalumab plus GemCis improved OS regardless of subsequent anticancer therapy use.

With regard to safety, serious adverse events (SAEs) among eLTS were similar between the two treatment arms and were less frequent than in the full safety analysis set.

“[A]fter 41.3 months of median follow-up, survival benefit with durvalumab plus GemCis was maintained vs placebo plus GemCis in participants with advanced BTC, with no meaningful changes in safety,” the investigators said.

“More participants taking durvalumab plus GemCis were eLTS, and there was a survival benefit associated with durvalumab plus GemCis use, regardless of the use of systemic anticancer therapy (SAT) vs placebo,” they added.

Targeted therapy

The number of TOPAZ-1 participants treated with approved targeted therapies (ie, FGFR and IDH1 inhibitors) as SATs was small, but those who received durvalumab showed consistent average time to death from starting subsequent SATs with the survival outcomes reported in previous studies. [Lancet Oncol 2020;21:671-684; Lancet Oncol 2020; 21:671-684; JAMA Oncol 2021;7:1669-1677]

“These results suggest durvalumab plus GemCis may not exert a negative impact on subsequent treatment with targeted therapies,” the researchers said.

“The previous updated safety analysis of TOPAZ-1 showed the incidence of SAEs and treatment-related SAEs was similar between treatment arms and consistent with the reports at previous analyses, suggesting the safety profile of durvalumab plus GemCis remains acceptable,” they added. [NEJM Evid 2022;1:EVIDoa2200015; Lancet Gastroenterol Hepatol 2024;9:694-704]