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Assessing the Safety, Efficacy, and Biomarkers of Durvalumab in Chemotherapy-Naïve Patients with Advanced Biliary Tract Cancer

August 2020, Vol 1, No 1

Immunotherapies have shown early promising efficacy in some patients with biliary tract cancer. Investigators evaluated the benefit of durvalumab (Imfinzi), a PD-L1 inhibitor, with or without tremelimumab, a CTLA-4 inhibitor, plus chemotherapy with gemcitabine and cisplatin as a first-line treatment for Korean patients with biliary tract cancer. The researchers also performed an extensive biomarker analysis.1

The study results were presented by Do-Youn Oh, MD, PhD, Medical Oncology, Seoul National University Hospital, South Korea, at the 2020 ASCO virtual annual meeting.

The patients were first enrolled in the biomarker cohort and received 1 cycle of gemcitabine 1000 mg/m2 plus cisplatin 25 mg/m2 on days 1 and 8, followed by gemcitabine plus cisplatin and durvalumab 1120 mg and tremelimumab 75 mg, every 3 weeks until disease progression. Subsequent patients were randomized to durvalumab plus gemcitabine and cisplatin (3-drug combination cohort) or to durvalumab plus tremelimumab, gemcitabine and cisplatin (4-drug combination cohort) until disease progression.

In all the cohorts, tumor biopsies were obtained before treatment, after 1 cycle, and at disease progression. Blood samples for circulating tumor cell DNA were obtained at every cycle. Tumor mutational burden was assessed during pretreatment tumor samples, and PD-L1 expression was assessed at tumor biopsy samples taken before and after treatment. A total of 121 patients were enrolled in the study.

The median follow-up durations were 28.5 months, 11.3 months, and 11.9 months in the biomarker cohort, the 3-drug combination cohort, and the 4-drug combination cohort, respectively.

The objective response rate (ORR) and the median overall survival (OS) were improved in the 3- and 4-drug combination cohorts compared with the biomarker cohort.

The ORR was 50.0 (95% confidence interval [CI], 32.1-67.9) in the biomarker cohort compared with 73.4 (95% CI, 60.5-86.3) in the 3-drug cohort and 73.3 (95% CI, 60.4-86.2) in the 4-drug cohort.

The median OS was 15.0 months (95% CI, 10.7-19.3) in the biomarker cohort compared with 18.1 months (95% CI, 11.3-24.9) in the 3-drug cohort and 20.7 months (95% CI, 13.8-27.6) in the 4-drug cohort.

By contrast, the median duration of response was longer with the biomarker cohort, at 11.0 months (95% CI, 3.9-11.8) compared with 9.8 months (95% CI, 8.1-11.4) in the 3-drug cohort and 9.1 months (95% CI, 4.5-15.0) in the 4-drug cohort.

Candidate biomarkers were identified that may be indicative of response to these therapies.

The most common (>10%) adverse events (of any grade) were nausea (59.5%), neutropenia (54.5%), and pruritus (55.4%). The most common grade 3 or 4 adverse events were neutropenia (50.4%), anemia (35.5%), and thrombocytopenia (16.5%).

The addition of immunotherapy to chemotherapy was tolerable and showed very promising efficacy. The combination of durvalumab plus chemotherapy with gemcitabine and cisplatin is being investigated in the global phase 3 TOPAZ-1 clinical trial.


  1. Oh DY, Lee KH, Lee DW, et al. Phase II study assessing tolerability, efficacy, and biomarkers for durvalumab (D) ± tremelimumab (T) and gemcitabine/cisplatin (GemCis) in chemo-naïve advanced biliary tract cancer (aBTC). J Clin Oncol. 2020;38(15_suppl):Abstract 4520.

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