The DEBATE Trial: Neoadjuvant Durvalumab Plus GemCis Versus GemCis Alone for Patients With Localized BTC

Researchers investigated the efficacy and safety of neoadjuvant durvalumab plus gemcitabine/cisplatin (GemCis) versus GemCis alone in patients with biliary tract cancer.

In the TOPAZ-1 study, durvalumab plus gemcitabine/cisplatin (GemCis) significantly improved efficacy in patients with advanced/metastatic biliary tract cancer (BTC) compared with GemCis alone; however, the efficacy of neoadjuvant durvalumab plus GemCis has not been studied.1 Changhoon Yoo, MD, PhD, presented results from the DEBATE trial, which investigated neoadjuvant durvalumab plus GemCis in patients with localized BTC.2

DEBATE was a multicenter, multidisciplinary, open-label, noncomparative, randomized, phase 2 trial that evaluated the efficacy and safety of durvalumab plus GemCis versus GemCis alone in treatment-naïve patients with localized BTC. Patients had histologically or cytologically confirmed localized BTC and an Eastern Cooperative Oncology Group performance status of 0/1 with adequate hematologic and organ function.2 Patients were randomly assigned 2:1 to receive either 4 cycles of neoadjuvant GemCis alone or durvalumab plus GemCis.2 Following surgery, 6 cycles of durvalumab were given regardless of treatment arm.2 The primary end point was R0 resection rate. Secondary end points included overall survival, progression-free survival (PFS), objective response rate (ORR), and safety. Circulating tumor DNA (ctDNA) analysis was performed using the GuardantOmni platform.2

A total of 45 patients were enrolled (n=31 in the durvalu-mab plus GemCis arm; n=14 in the GemCis arm).2 Intrahepatic cholangiocarcinoma (n=18, 40%) was the most common primary tumor site, and 69% (n=31) had clinical stage III disease.2 The ORR was 36% (n=11) in the durvalumab plus GemCis arm and 7% (n=1) in the GemCis arm.2 In the durvalumab plus GemCis and GemCis arms, surgical exploration was performed in 68% (n=21) and 43% (n=6), curative-intent resection (R0+R1) was performed in 61% (n=19) and 43% (n=6), and R0 resection was performed in 48% (n=15) and 43% (n=6), respectively.2 Median PFS was 15.2 (95% confidence interval [CI], 8.8-23.3) months in the durvalumab plus GemCis arm and not achieved (NA) in the GemCis-alone arm.2 Overall survival was 6.2 (95% CI, 2.7-NA) months in the durvalumab plus GemCis arm and 25.6 (95% CI, 15.1-NA) months in the GemCis arm. Some of the most common grade 3/4 adverse events included anemia (durvalumab plus GemCis: 3 [10%]; GemCis: 0), neutropenia (durvalumab plus GemCis: 11 [36%]; GemCis: 9 [64%]), and thrombocytopenia (durvalumab plus GemCis: 1 [3%]; GemCis: 1 [7%]).2

A higher surgical resection rate was seen in patients treated with neoadjuvant durvalumab plus GemCis, and surgical resection was associated with improved survival.2 The analysis of ctDNA was shown to be a useful method for assessing actionable target gene alterations in early BTC.2


  1. Oh DY, He AR, Qin S, et al. Durvalumab plus gemcitabine and cisplatin in advanced biliary tract cancer. NEJM Evid. 2022;1(8).
  2. Yoo C, Park JO, Kim K-P, et al. Neoadjuvant durvalumab plus gemcitabine and cisplatin (D+GemCis) versus GemCis alone for localized biliary tract cancer (BTC): results of a randomized, multicenter, open-label, phase 2 trial (DEBATE). Presented at: ESMO Congress 2023, October 20-24, 2023; Madrid, Spain.

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