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Ken Garber, Promising Early Results for Immunotherapy–Antiangiogenesis Combination, JNCI: Journal of the National Cancer Institute, Volume 106, Issue 11, November 2014, dju392, https://doi.org/10.1093/jnci/dju392
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Although immune checkpoint blockade has become standard care in metastatic melanoma, angiogenesis inhibitors have had limited success. Now researchers have combined the two.
July’s Cancer Immunology Research reported a phase I study combining ipilimumab and bevacizumab (doi:10.1016/j.ctrv.2014.06.012). Among 46 patients, the combined therapy yielded a 19.6% objective response rate and a median survival of 25.1 months—roughly twice expectations for ipilimumab alone in metastatic melanoma. And, at least by modern immunotherapy standards, patients tolerated the combination well.
“A 25-month survival in a pretreated population is pretty darned impressive,” said Jeffrey Weber, M.D., Ph.D., an oncologist at Moffitt Cancer Center in Tampa, Fla. “It looked awfully promising. And certainly it’s something that needs to be pursued in a proper phase II study,” This study is under way.
When Dana–Farber Cancer Institute oncologist F. Stephen Hodi Jr., M.D., conceived the phase I trial, he envisioned more than just combining two anticancer modalities—he sought synergy. Biopsy samples taken after treatment reveal a double paradox: Immunotherapy can be antiangiogenic, and antiangiogenesis can stimulate the immune system. So combining the treatments should enhance both antitumor effects. Several years ago, Hodi’s team examined posttreatment biopsy samples from patients taking ipilimumab following a cancer vaccine. The immune system specifically targeted tumor blood vessels, for still-unknown reasons.
