Ramez N. Eskander, MD, is an assistant professor in the Departments of Obstetrics, Gynecology, and Reproductive Sciences at the University of California (UC) San Diego School of Medicine; as well as the director for oncology of the clinical trials office at the UC San Diego Moores Cancer Center

Ramez N. Eskander, MD, assistant clinical professor, Department of Reproductive Medicine, University of California, San Diego Moores Cancer Center, discusses the need for more effective biomarkers in the treatment of patients with ovarian cancer.

There are several challenges that stand in the way of moving the needle forward in this space, but arguably the biggest one is the need for the identification of more biomarkers predictive of response or of prognostic value. Currently, researchers are testing combination approaches in all-comers, even expanding this research into patients with high-grade serous tumors. This makes it difficult for oncologists to determine which specific patient subsets are more likely to benefit from emerging therapies.

 and homologous recombination deficiency have already been established as effective biomarkers, but research is lagging beyond that, Eskander says. Immunotherapy is being integrated into treatment in combination with other modalities like PARP inhibitors and antiangiogenic agents, but Eskander notes that physicians are not yet sure which patients should get which combination. Until biomarkers are discovered, the field may continue running into challenges developing more effective treatment strategies for these patients.

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Dr. Eskander on Need for Biomarkers in Ovarian Cancer

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.

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

Ramez N. Eskander, MD

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Dr. Eskander on Need for Biomarkers in Ovarian Cancer

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