Dr. Eskander on Combination Approaches With Immunotherapy in Ovarian Cancer

Ramez N. Eskander, MD
Published: Thursday, Jan 31, 2019



Ramez N. Eskander, MD, assistant clinical professor, Department of Reproductive Medicine, University of California, San Diego Moores Cancer Center, discusses the investigation of combinatorial approaches with immunotherapy in the treatment of patients with ovarian cancer.

Although single-agent immunotherapy has been largely ineffective, immunotherapy could still have a role in the space when used in combination with other already effective drugs, Eskander says. For example, combining checkpoint inhibitors with the antiangiogenic agent bevacizumab (Avastin) could hold promise. Researchers know that VEGF has an immune-inhibitory function, and that VEGF signaling leads to an increase in regulatory T cells and prevents effector T cells from migrating to the tumor microenvironment. Combining these mechanisms of action with standard chemotherapy might lead to better responses—and this is already being tested in ongoing studies.

Additionally, researchers are looking at combining immunotherapy with the 3 FDA-approved PARP inhibitors: rucaparib (Rubraca), olaparib (Lynparza), and niraparib (Zejula). PARP inhibitors are inciters of DNA damage and tumor-associated antigens. Could stimulating the tumor mutational burden cause the tumor to become immunogenic? Early data from the TOPACIO study suggested benefit, but the magnitude of this benefit remains unclear.
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Ramez N. Eskander, MD, assistant clinical professor, Department of Reproductive Medicine, University of California, San Diego Moores Cancer Center, discusses the investigation of combinatorial approaches with immunotherapy in the treatment of patients with ovarian cancer.

Although single-agent immunotherapy has been largely ineffective, immunotherapy could still have a role in the space when used in combination with other already effective drugs, Eskander says. For example, combining checkpoint inhibitors with the antiangiogenic agent bevacizumab (Avastin) could hold promise. Researchers know that VEGF has an immune-inhibitory function, and that VEGF signaling leads to an increase in regulatory T cells and prevents effector T cells from migrating to the tumor microenvironment. Combining these mechanisms of action with standard chemotherapy might lead to better responses—and this is already being tested in ongoing studies.

Additionally, researchers are looking at combining immunotherapy with the 3 FDA-approved PARP inhibitors: rucaparib (Rubraca), olaparib (Lynparza), and niraparib (Zejula). PARP inhibitors are inciters of DNA damage and tumor-associated antigens. Could stimulating the tumor mutational burden cause the tumor to become immunogenic? Early data from the TOPACIO study suggested benefit, but the magnitude of this benefit remains unclear.

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