Randomized phase II/III clinical trial of elpamotide for patients with advanced pancreatic cancer: PEGASUS‐PC Study |
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| Authors: | Hiroki Yamaue Takuya Tsunoda Masaji Tani Motoki Miyazawa Kenji Yamao Nobumasa Mizuno Takuji Okusaka Hideki Ueno Narikazu Boku Akira Fukutomi Hiroshi Ishii Shinichi Ohkawa Masayuki Furukawa Hiroyuki Maguchi Masafumi Ikeda Yosuke Togashi Kazuto Nishio Yasuo Ohashi |
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| Affiliation: | 1. Second Department of Surgery Wakayama Medical University, Wakayama, Japan;2. Department of Gastroenterology Aichi Cancer Center Hospital, Aichi, Japan;3. Hepatobiliary and Pancreatic Oncology Division National Cancer Center Hospital, Tokyo, Japan;4. Department of Gastroenterology Shizuoka Cancer Center, Shizuoka, Japan;5. Hepatobiliary and Pancreatic Division Cancer Institute Hospital, Tokyo, Japan;6. Hepatobiliary and Pancreatic Medical Oncology Division Kanagawa Cancer Center Hospital, Kanagawa, Japan;7. Department of Gastroenterology National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan;8. Center for Gastroenterology Teine‐Keijinkai Hospital, Hokkaido, Japan;9. Division of Hepatobiliary and Pancreatic Oncology National Cancer Center Hospital East, Chiba, Japan;10. Dept Genome Biology Kinki University School of Medicine, Osaka, Japan;11. Department of Integrated Science and Engineering for Sustainable society Chuo University, Tokyo, Japan |
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| Abstract: | Gemcitabine is a key drug for the treatment of pancreatic cancer; however, with its limitation in clinical benefits, the development of another potent therapeutic is necessary. Vascular endothelial growth factor receptor 2 is an essential target for tumor angiogenesis, and we have conducted a phase I clinical trial using gemcitabine and vascular endothelial growth factor receptor 2 peptide (elpamotide). Based on the promising results of this phase I trial, a multicenter, randomized, placebo‐controlled, double‐blind phase II/III clinical trial has been carried out for pancreatic cancer. The eligibility criteria included locally advanced or metastatic pancreatic cancer. Patients were assigned to either the Active group (elpamotide + gemcitabine) or Placebo group (placebo + gemcitabine) in a 2:1 ratio by the dynamic allocation method. The primary endpoint was overall survival. The Harrington–Fleming test was applied to the statistical analysis in this study to evaluate the time‐lagged effect of immunotherapy appropriately. A total of 153 patients (Active group, n = 100; Placebo group, n = 53) were included in the analysis. No statistically significant differences were found between the two groups in the prolongation of overall survival (Harrington–Fleming P‐value, 0.918; log–rank P‐value, 0.897; hazard ratio, 0.87, 95% confidence interval [CI], 0.486–1.557). Median survival time was 8.36 months (95% CI, 7.46–10.18) for the Active group and 8.54 months (95% CI, 7.33–10.84) for the Placebo group. The toxicity observed in both groups was manageable. Combination therapy of elpamotide with gemcitabine was well tolerated. Despite the lack of benefit in overall survival, subgroup analysis suggested that the patients who experienced severe injection site reaction, such as ulceration and erosion, might have better survival. |
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| Keywords: | Advanced pancreatic cancer elpamotide immunotherapy peptide vaccine phase II/III |
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