Q&A: ‘Promising’ immunotherapies may treat platinum-resistant ovarian cancer

During their lifetime, one in 70 women will receive a diagnosis of ovarian cancer, which is the second most common gynecologic cancer in the United States, according to Memorial Sloan Kettering Cancer Center.

Among these, 15% to 30% will have platinum-resistant or refractory ovarian cancer, data show.

Although the FDA granted fast track designation to a combination therapy for platinum-resistant disease in May, studies are still ongoing to identify other potential treatment options.

Healio spoke with Ira Winer, MD, PhD, an associate professor in the division of gynecologic oncology at Wayne State University in Detroit, to learn more about what treatments show the most promise for platinum-resistant ovarian cancer.

Healio: Why is platinum-resistant ovarian cancer (PROC) difficult to treat?

Winer: Taking a step back, ovarian cancer in general can be a difficult disease to treat. This is largely due to the fact that it is a difficult disease to recognize and diagnose because the symptoms can be vague and are often mild. Once a patient is diagnosed with ovarian cancer, they will be treated with platinum-based chemotherapies combined with surgery up front. Maintenance strategies are also utilized to prevent recurrent disease. Unfortunately, still, approximately 80% of patients will recur ultimately. Once platinum resistance is identified, very few conventional agents offer significant response as the disease becomes resistant to prototypical/conventional DNA-damaging agents.

Healio: What are the current options available to patients?

Winer: With a PROC diagnosis, the standard treatment has been non-platinum chemotherapy in combination with Avastin (bevacizumab, Genentech), but this has been shown to provide only a low likelihood of long-term effectiveness for patients. Typically, we are looking at a response of about 10% to 30% for most patients (especially in later lines), and progression is typically quick with a median survival — still only about 12 months once PROC is diagnosed. Hence, a need for new therapy development is critical.

Healio: How does immuno-oncology therapy work?

Winer: There are several types of immunotherapies used in the oncology field, including immune checkpoint inhibitors, T-cell transfer therapy, [chimeric antigen receptor] T-cell therapy, monoclonal antibodies and other immune system modulators, often in combination with checkpoint inhibitors, to name a few. Immunotherapies harness the power of the patient’s immune system to identify and fight cancer. Each of these therapies is designed to activate or boost the patient’s immune system in a different way, but most current immuno-oncology approaches involve improving the ability and/or expanding the number of certain cancer-fighting immune cells (such as CD8+ T cells and/or natural killer cells) in the tumor microenvironment to recognize and attack tumor cells.

Healio: What novelty can immuno-oncology therapy bring to the treatment of PROC?

Winer: Although immune checkpoint inhibitors are approved to treat several types of cancer, they have shown limited success in ovarian cancer to date (10% to 15% response rate) in single-agent trials. Therefore, new mechanistic approaches and combinations are needed to more effectively harness the power of the immune system to treat this disease. In particular, approaches that activate the antitumor effects of immune cells while avoiding immunosuppression may have potential in PROC.

Because the unmet need is great, various new potential therapeutic options are being explored including, but not limited to, combining antibody-drug conjugates (ADCs) with or without immuno-oncology agents, interleukin (IL)-2s, IL-15s and others such as [chimeric antigen receptor] T-cell therapy. In fact, the first ADC for PROC was approved only this past week, although this was a non-immunotherapy-based platform!

One investigational approach that is currently recruiting in phase 3 trials is evaluating IL-2, a cytokine that binds to a receptor on the surface of certain immune cell types, promoting cell proliferation and effector activity. IL-2 may also potentiate the activity of other immunotherapies, and for this reason, IL-2-based therapies are under investigation in PROC as monotherapy, as well as in combination with immune checkpoint blockade.

Healio: Is there anything else about platinum-resistant cancer and immuno-oncology therapy that you would like to add?

Winer: The current immuno-oncology therapy landscape is one of innovation and advancement. We are seeing many promising investigational immunotherapies for the treatment of PROC and have hope that in the near future the types of treatments available to PROC patients will be more effective leading to better patient outcomes. For now, the focus is on the research — both preclinical and clinical — and basic and translational investigators are working as quickly as possible to bring this future to reality.

References:

• Lou E, et al. JAMA Oncol. 2019;doi:10.1001/jamaoncol.2019.1943.
• Memorial Sloan Kettering Cancer Center. Ovarian Cancer. https://www.mskcc.org/cancer-care/types/ovarian?msclkid=46ce021766ab13aec7b161624f6dbedd&utm_source=bing&utm_medium=cpc&utm_campaign=GYN_Ovarian%20%5BKNOWN%5D&utm_term=ovarian%20cancer&utm_content=General. Accessed Nov. 16, 2022.