Dr Cannon on Suboptimal Efficacy Findings With Immunotherapy in Ovarian Cancer

Martin Cannon, PhD, professor, microbiology and immunology, the University of Arkansas for Medical Sciences (UAMS), UAMS College of Medicine, discusses data seen with immune checkpoint inhibitors in patients with ovarian cancer and why these agents are not as effective in this population as they are in other cancer types.

Findings from a phase 2 trial (UMIN000005714) that were published in the Journal of Clinical Oncology in 2015 showed that patients with platinum-resistant ovarian cancer who received nivolumab (Opdivo) achieved a 15% overall response rate (ORR; 95% CI, 3.2%-37.9%). Among the 3 patients who responded, 2 achieved a complete response, and 1 achieved a partial response. These data did not support the use of immune checkpoint inhibitors in patients with platinum-resistant disease, Cannon explains.

The pivotal phase 2 KEYNOTE-100 trial (NCT02674061), published in 2019 in Annals of Oncology by Ursula A. Matulonis, MD, of Dana-Farber Cancer Institute, and colleagues, evaluated the efficacy and safety of pembrolizumab (Keytruda) in 2 cohorts of patients with advanced recurrent ovarian cancer. Cohort A consisted of patients who had received 1 to 3 prior lines of treatment with a platinum-free interval or treatment-free interval of 3 to 12 months. Cohort B was comprised of patients who had received between 4 and 6 prior lines of therapy with a platinum-free interval or treatment-free interval of at least 3 months. The ORRs in cohorts A and B, respectively, were 7.4% and 9.9%. These findings indicated that immune checkpoint inhibitors were ineffective in patients with ovarian cancer, Cannon says.

Despite the low response rates seen with immune checkpoint inhibitors in patients with ovarian cancer, these agents are effective in several other cancers, Cannon notes. Importantly, immune checkpoint inhibitors do not target the cancer itself, and instead target T-cell responses, Cannon explains. Therefore, these agents are not effective in patients whose tumors do not have T-cell responses, Cannon emphasizes.

Ovarian cancers may not have enough antitumor T-cell response for immune checkpoint inhibitors to be effective, according to Cannon. These cancers may have low tumor mutational burdens and lack T cell–stimulating antigens, or the tumors may have microenvironments with immune suppression, Cannon says. Ovarian cancers may have T cells, including highly immunosuppressive regulatory T cells. However, these T cells need to be expressed before immune checkpoint inhibitors, such as nivolumab or pembrolizumab, can be effective, Cannon concludes.