Durvalumab With or Without Tremelimumab in Metastatic Pancreatic Cancer
In the first stage of a phase II trial reported in JAMA Oncology, O’Reilly et al found poor activity of durvalumab with or without tremelimumab in metastatic pancreatic ductal adenocarcinoma. Owing to the lack of efficacy, study expansion was not pursued.
The lead-in open-label safety phase of the trial (part A) included 65 patients from 21 sites in six countries who had previously received only one first-line fluorouracil- or gemcitabine-based treatment for recurrent or metastatic disease. Patients were randomly assigned between November 2015 and March 2017 to receive durvalumab at 1,500 mg every 4 weeks plus tremelimumab at 75 mg every 4 weeks for 4 cycles, followed by durvalumab at 1,500 mg every 4 weeks (n = 32); or durvalumab monotherapy at 1,500 mg every 4 weeks (n = 33) for up to 12 months or until disease progression or unacceptable toxicity. The criterion for continuing the study in an expansion phase (part B) was an objective response rate of 10% in either group in part A.
Response and Adverse Events
Objective response was observed in 3.1% of patients in the durvalumab/tremelimumab group and in no patients in the durvalumab monotherapy group.
Treatment-related adverse events of any grade occurred in 34% of the durvalumab/tremelimumab group and 21% of the durvalumab monotherapy group, with the most common being fatigue, diarrhea, and pruritus in both groups. Grade ≥ 3 treatment-related adverse events occurred in 22% vs 6%, with the most common in the durvalumab/tremelimumab group being diarrhea (9%, vs 0% in the monotherapy group) and fatigue (6% vs 0%). Overall, treatment-related adverse events resulted in discontinuation of treatment in 6% of patients.
The investigators concluded: “Treatment was well tolerated, and the efficacy of durvalumab plus tremelimumab therapy and durvalumab monotherapy reflected a population of patients with metastatic pancreatic ductal adenocarcinoma who had poor prognoses and rapidly progressing disease. Patients were not enrolled in part B because the threshold for efficacy was not met in part A.”
Eileen M. O’Reilly, MD, of Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, is the corresponding author for the JAMA Oncology article.
Disclosure: The study was funded by AstraZeneca. For full disclosures of the study authors, visit jamanetwork.com.
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