Early Study Shows Improved Survival With Radioimmunotherapy/Gemcitabine Combination in Patients With Advanced Pancreatic Ductal Cancer
A randomized phase Ib study of a combination of low radiosensitizing doses of gemcitabine and fractionated doses of 90Y-clivatuzumab tetraxetan in patients with metastatic pancreatic ductal cancer who had received at least two prior systemic therapies, has found a significant survival advantage in patients receiving the combination therapy compared with patients receiving radioimmunotherapy alone. The study by Picozzi et al was presented at the American Association for Cancer Research (AACR) conference on Pancreatic Cancer: Innovation in Research and Treatment, held in New Orleans from May 18 to 21.
Study Methods and Findings
The study included 58 patients (33 men and 25 women) with metastatic pancreatic ductal cancer who received at least two prior therapies. The median age was 63.5 years. Patients were randomly assigned to either arm A (29 patients) or arm B (29 patients).
Patients in both arms received 6.5 mCi/m2 90Y-clivatuzumab tetraxetan for 3 weeks, divided into multiple smaller doses per cycle. Patients from arm A also received low-dose gemcitabine for 1 week and then in combination with the radioimmunotherapy for 3 weeks in each cycle. Treatment continued for up to nine cycles, with 4-week delays in between. The goal of the study was to determine the safety and efficacy of this approach and to evaluate the contribution of low-radiosensitizing doses of gemcitabine to the regimen.
A total of 27 and 26 patients from arms A and B, respectively, completed at least one cycle of treatment; 12 and 11 patients completed two or more cycles of treatment, with the remainder terminating treatment due to disease progression or clinical deterioration, but not treatment toxicity.
The researchers found that patients from arm A were 45% more likely to live longer compared with patients from arm B. For patients who received only one treatment cycle, there was little survival difference between both arms (3.9 months in arm A vs 2.8 months in arm B). However, the median overall survival for arm A vs arm B increased to 7.9 months vs 3.4 months with multiple cycles (P = .004), and three patients in arm A are still being observed (11–17 months).
Side effects were minimal, and the only clinically significant side effect that occurred with any frequency was a decrease in blood counts.
Clinical Implications
“The thinking here [was] that radiotherapy can be an effective therapy for pancreas cancer like it is for most cancers,” said Vincent J. Picozzi, Jr, MD, lead author of the study and Director of the Pancreas Center of Excellence at the Virginia Mason Medical Center’s Digestive Disease Institute, at a press conference announcing the study results.
According to Dr. Picozzi, the significance of the study is threefold. First, it demonstrates the feasibility of both clinical research and treatment in a group of patients with pancreatic cancer for whom there is no standard of care. Second, the use of a radiolabeled antibody either with or without gemcitabine can be accomplished safely in this group of patients. And, third, the study suggests the potential efficacy of the radiolabeled antibody and gemcitabine combination.
A larger, randomized phase III clinical trial is now accruing patients to confirm these study results.
The study was funded by Immunomedics Inc. Dr. Picozzi reported no conflicts of interest.
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