7/31/2019
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`Durvalumab With or Without Tremelimumab for Patients With Metastatic Pancreatic Ductal Adenocarcinoma: A Phase 2 Randomized Cli…
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`PubMed
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`Format: Abstract
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`Full text links
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`JAMA Oncol. 2019 Jul 18. doi: 10.1001/jamaoncol.2019.1588. [Epub ahead of print]
`Durvalumab With or Without Tremelimumab for Patients With
`Metastatic Pancreatic Ductal Adenocarcinoma: A Phase 2
`Randomized Clinical Trial.
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`O'Reilly EM , Oh DY , Dhani N , Renouf DJ , Lee MA , Sun W , Fisher G , Hezel A , Chang SC , Vlahovic G ,
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`Takahashi O , Yang Y , Fitts D , Philip PA .
`Author information
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`Abstract
`New therapeutic options for patients with metastatic pancreatic ductal
`IMPORTANCE:
`adenocarcinoma (mPDAC) are needed. This study evaluated dual checkpoint combination therapy in
`patients with mPDAC.
`To evaluate the safety and efficacy of the anti-PD-L1 (programmed death-ligand 1)
`OBJECTIVE:
`antibody using either durvalumab monotherapy or in combination with the anticytotoxic T-
`lymphocyte antigen 4 antibody using durvalumab plus tremelimumab therapy in patients with
`mPDAC.
`Part A of this multicenter, 2-part, phase 2 randomized
`DESIGN, SETTING, AND PARTICIPANTS:
`clinical trial was a lead-in safety, open-label study with planned expansion to part B pending an
`efficacy signal from part A. Between November 26, 2015, and March 23, 2017, 65 patients with
`mPDAC who had previously received only 1 first-line fluorouracil-based or gemcitabine-based
`treatment were enrolled at 21 sites in 6 countries. Efficacy analysis included the intent-to-treat
`population; safety analysis included patients who received at least 1 dose of study treatment and for
`whom any postdose data were available.
`Patients received durvalumab (1500 mg every 4 weeks) plus tremelimumab (75
`INTERVENTIONS:
`mg every 4 weeks) combination therapy for 4 cycles followed by durvalumab therapy (1500 mg
`every 4 weeks) or durvalumab monotherapy (1500 mg every 4 weeks) for up to 12 months or until
`the onset of progressive disease or unacceptable toxic effects.
`Safety and efficacy were measured by objective response
`MAIN OUTCOMES AND MEASURES:
`rate, which was used to determine study expansion to part B. The threshold for expansion was an
`objective response rate of 10% for either treatment arm.
`Among 65 randomized patients, 34 (52%) were men and median age was 61 (95% CI,
`RESULTS:
`37-81) years. Grade 3 or higher treatment-related adverse events occurred in 7 of 32 patients (22%)
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`https://www.ncbi.nlm.nih.gov/pubmed/31318392
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`7/31/2019
`Durvalumab With or Without Tremelimumab for Patients With Metastatic Pancreatic Ductal Adenocarcinoma: A Phase 2 Randomized Cli…
`receiving combination therapy and in 2 of 32 patients (6%) receiving monotherapy; 1 patient
`randomized to the monotherapy arm did not receive treatment owing to worsened disease. Fatigue,
`diarrhea, and pruritus were the most common adverse events in both arms. Overall, 4 of 64 patients
`(6%) discontinued treatment owing to treatment-related adverse events. Objective response rate was
`3.1% (95% CI, 0.08-16.22) for patients receiving combination therapy and 0% (95% CI, 0.00-10.58)
`for patients receiving monotherapy. Low patient numbers limited observation of the associations
`between treatment response and PD-L1 expression or microsatellite instability status.
`Treatment was well tolerated, and the efficacy of durvalumab
`CONCLUSION AND RELEVANCE:
`plus tremelimumab therapy and durvalumab monotherapy reflected a population of patients with
`mPDAC 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.
`ClinicalTrials.gov identifier: NCT02558894.
`TRIAL REGISTRATION:
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`PMID: 31318392 DOI: 10.1001/jamaoncol.2019.1588
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`Secondary source ID
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`LinkOut - more resources
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`https://www.ncbi.nlm.nih.gov/pubmed/31318392
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