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

References

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.