Advanced biliary tract cancer remains difficult to treat, and first-line chemotherapy choices often vary according to patient fitness, tolerability, and local practice. The phase IIIb TOURMALINE study evaluated first-line durvalumab combined with different gemcitabine-based chemotherapy regimens in patients with advanced biliary tract cancer.
The article, titled “Durvalumab with gemcitabine-based chemotherapy regimens in advanced biliary tract cancer: primary results from the phase IIIb TOURMALINE study,” was published on July 5, 2026, in the Journal of Hepatology.
Authors: Do-Youn Oh, Masafumi Ikeda, Teresa Macarulla, Aiwu Ruth He, Joon Oh Park, Masayuki Kitano, Guido Giordano, Kyu-pyo Kim, Thomas Wirth, David Tai, Mohamed Bouattour, Tiziana Pressiani, Farshid Dayyani, Angela Lamarca, Ugochinyere Emeribe, Susanne Radke, Peng Sun, Boris Baur, and Arndt Vogel.
Background
Durvalumab plus gemcitabine and cisplatin became an established first-line standard for advanced biliary tract cancer after TOPAZ-1 showed an overall survival benefit with the addition of immunotherapy.
However, chemotherapy backbones used in practice vary across regions and patient groups. Cisplatin may not be suitable for every patient, and alternative gemcitabine-based regimens are often used in routine care. TOURMALINE was designed to explore whether durvalumab could be combined safely with several gemcitabine-based regimens in a broader, close-to-real-world population, including patients with poorer prognostic features such as ECOG performance status 2.
Read more about Time Toxicity in Advanced Biliary Tract Cancer on OncoDaily.
TOURMALINE Study Design
TOURMALINE is a phase IIIb, single-arm, open-label, international, multicentre study. The trial included adults with histologically confirmed unresectable advanced or metastatic biliary tract cancer, including intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, gallbladder carcinoma, and ampulla of Vater carcinoma.
Patients had ECOG performance status 0–2, no prior systemic treatment for advanced disease, and were not eligible for locoregional therapy.
Participants received durvalumab 1500 mg intravenously with investigator’s choice of one of seven predefined gemcitabine-based chemotherapy regimens. These included gemcitabine alone; gemcitabine combined with carboplatin, oxaliplatin, cisplatin, or S-1; and triplet regimens with gemcitabine, cisplatin, and either S-1 or albumin-bound paclitaxel. Gemcitabine plus cisplatin as a doublet was used only in participants with ECOG performance status 2.
The first durvalumab infusion was given over 60 minutes. If tolerated, subsequent infusions were given over 30 minutes. The primary endpoint was the incidence of grade 3/4 adverse events possibly related to study treatment within 6 months after durvalumab initiation. Secondary endpoints included progression-free survival, overall survival, objective response rate, duration of response, disease control rate at 24 and 32 weeks, duration of treatment, safety, and health-related quality of life, which will be reported in a future publication.
Read more about Durvalumab (Imfinzi) on OncoDaily.
Patient Population
As of the September 17, 2025 data cutoff, 142 patients had at least 6 months of follow-up and had received at least one dose of treatment. The median age was 68 years. Most patients had metastatic disease, representing 72.5% of the study population. Intrahepatic bile duct cancer was the most common primary tumour location, reported in 51.4% of patients, followed by gallbladder cancer in 24.6%. A total of 22 patients, or 15.5%, had ECOG performance status 2 at baseline.
Safety Results
Grade 3/4 adverse events possibly related to treatment within 6 months occurred in 50.7% of patients. Grade 3/4 adverse events possibly related to treatment at any time occurred in 53.5% of patients. Any adverse event was reported in all patients, while serious adverse events occurred in 47.2%.
The most common adverse events were anaemia, nausea, constipation, and decreased neutrophil count. The most frequent grade 3/4 adverse events were anaemia, decreased neutrophil count, and decreased platelet count.
Adverse events led to discontinuation of any study treatment in 16.9% of patients. Importantly, shortening the durvalumab infusion time after the first cycle did not appear to increase infusion-related reactions. Infusion-related adverse events occurred in 5.6% of patients, and infusion-related adverse events possibly related to durvalumab were reported in 3.5%.
Efficacy Results
Median progression-free survival in the overall population was 7.39 months. Median overall survival was 13.50 months.
The objective response rate was 33.1%, including 3 complete responses and 44 partial responses. Disease control was reported in 66.2% of patients at 24 weeks and 57.0% at 32 weeks. Median duration of response was 11.66 months.
In the ECOG performance status 2 subgroup, median progression-free survival was 9.07 months, median overall survival was not estimable, and the objective response rate was 50.0%. These findings were encouraging, although the subgroup was small and should be interpreted with caution.
Clinical Meaning
TOURMALINE supports the feasibility of combining durvalumab with several gemcitabine-based chemotherapy backbones in advanced biliary tract cancer, including in a broader population than that studied in TOPAZ-1.
The study also offers practical reassurance that, after a tolerated first 60-minute infusion, subsequent durvalumab infusions may be administered over 30 minutes without an apparent increase in infusion-related reactions.
Because TOURMALINE was single-arm and treatment selection was based on investigator choice, the results should not be used to compare the chemotherapy regimens directly. Still, the data help address an important real-world question: how durvalumab-based treatment may fit when gemcitabine-cisplatin is not the only backbone used in practice.
The full article is available in Journal of Hepatology.
Find more videos on OncoDaily YouTube TV.