J Gynecol Oncol.  2018 Nov;29(6):e93. 10.3802/jgo.2018.29.e93.

Checkpoint-inhibition in ovarian cancer: rising star or just a dream?

• Pietzner K
• Nasser S
• Alavi S
• Darb-Esfahani S
• Passler M
• Muallem MZ
• Sehouli J

• KMID: 2431238
• DOI: http://doi.org/10.3802/jgo.2018.29.e93

Abstract

The introduction of checkpoint inhibitors revolutionized immuno-oncology. The efficacy of traditional immunotherapeutics, like vaccines and immunostimulants was very limited due to persistent immune-escape strategies of cancer cells. Checkpoint inhibitors target these escape mechanisms and re-direct the immune system to anti-tumor toxicity. Phenomenal results have been reported in entities like melanoma, where no other therapy was able to demonstrate survival benefit, before the introduction of immunotherapeutics. The first experience in ovarian cancer (OC) was reported for nivolumab, a fully human anti-programmed cell death protein 1 (PD1) antibody, in 2015. While the data are extraordinary for a mono-immunotherapeutic agent and very promising, they do not match up to the revolutionary results in entities like melanoma. The key to exceptional treatment response in OC, could be the identification of the most immunogenic patients. We hypothyse that BRCA mutation could be a predictor of improved response in OC. The underlying DNA-repair-deficiancy should result in increased immunogenicity because of higher mutational load and more neoantigen presentation. This hypothesis was not tested to date and should be subject to future trials. The present article gives an overview of the immunologic background of checkpoint inhibition (CI). It presents current data on nivolumab and other checkpoint-inhibitors in solid tumors and OC specifically and depicts important topics in the management of this novel substance group, such as side effect control, diagnostic PD-1/programmed cell death-ligand 1 (PD-L1) expression assessment and management of pseudoprogression.

Keyword

Checkpoint-Inhibition; Ovarian Cancer; Immunooncology; Gynecologic Oncology; BRCA Mutation

MeSH Terms

Adjuvants, Immunologic
Cell Death
Dreams*
Humans
Immune System
Melanoma
Ovarian Neoplasms*
United Nations
Vaccines
Adjuvants, Immunologic
Vaccines