Disclosures: Oh reports receiving research grants from Array, AstraZeneca, BeiGene, Eli Lilly, Merck Sharp & Dohme, Novartis and Servier. Please see the study for all other authors’ relevant financial disclosures.
Gemcitabine and cisplatin plus durvalumab, with or without tremelimumab, produced favorable outcomes as first-line treatment for advanced biliary tract cancer, according to research.
“Immune checkpoint inhibitors have been assessed in biliary tract cancer and have shown clinical activity,” Do-Youn Oh, MD, of the division of medical oncology at Seoul National University Hospital, and colleagues wrote in The Lancet. “Furthermore, chemotherapeutic agents, including gemcitabine and cisplatin, have been shown to induce immunomodulatory effects. Study findings from 2019 in patients with biliary tract cancer suggest that combinations of chemotherapy with immunotherapy might prolong survival compared with either of the approaches alone.”
To assess gemcitabine and cisplatin in combination with durvalumab, with or without tremelimumab, as first-line treatment for advanced biliary tract cancer, Oh and colleagues conducted an open-label, phase 2 study at Seoul National University Hospital. Between March 2017 and February 2020 they enrolled 124 adults with histologically proven unresectable or recurrent biliary tract cancer, all of whom had at least one measurable lesion based on the Response Evaluation Criteria in Solid Tumors, an Eastern Cooperative Oncology Group performance status of 0 or 1, life expectancy of 12 weeks or longer, and adequate organ and bone marrow function.
All participants received gemcitabine (1,000 mg/m²) plus cisplatin (25 mg/m²) on days 1 and 8 every 3 weeks, followed by chemotherapy plus durvalumab (1,120 mg) and tremelimumab (75 mg) on day 1 of each 3-week cycle, starting with the second cycle (chemotherapy followed by chemotherapy plus durvalumab and tremelimumab group, n = 30). The protocol was amended after enrollment to add chemotherapy plus durvalumab without tremelimumab (chemotherapy plus durvalumab group, n = 47) and with tremelimumab ( chemotherapy plus durvalumab and tremelimumab group, n = 47).
According to study results, 66% of the total cohort achieved the primary endpoint of an objective response, which included 50% of patients in the chemotherapy followed by chemotherapy plus durvalumab and tremelimumab group; 72% in the chemotherapy plus durvalumab group; and 70% in the chemotherapy plus durvalumab and tremelimumab group. Disease control was achieved in 98% of all patients.
The most common grade 3 and 4 adverse events were decreased neutrophil count, anemia and decreased platelet count, and no adverse events led to discontinuation or death.
“Overall, the addition of immunotherapy to chemotherapy in three different treatment combinations showed promising efficacy and acceptable safety profiles,” Oh and colleagues concluded. “These findings provided a basis for the ongoing, randomized, phase 3 TOPAZ-1 study, evaluating chemotherapy plus durvalumab versus gemcitabine and cisplatin alone as first-line treatment in patients with advanced biliary tract cancer.”