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17.02.2020 | short review | Ausgabe 2/2020 Open Access

memo - Magazine of European Medical Oncology 2/2020

Current state and perspectives of checkpoint inhibitors in ovarian cancer treatment

Zeitschrift:
memo - Magazine of European Medical Oncology > Ausgabe 2/2020
Autoren:
MD Thomas Bartl, MD Valentina Paspalj, MD Assoc.-Prof. PD Stephan Polterauer, MD Assoc.-Prof. PD Christoph Grimm
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Summary

The introduction of checkpoint inhibitors (CPI) has set a paradigm shift within the therapies for a variety of advanced solid tumors. By altering key regulators of cellular immune response, so-called immune checkpoints, CPIs modulate peripheral cancer immune tolerance to induce cancer-targeted immune reactions. Response rates, however, vary significantly between different solid tumor types. A certain efficacy of CPIs has been described for gynecological malignancies, as the KEYNOTE-028 study reported an objective response rate (ORR) of 13.0% (95% confidence interval [CI] 2.8–33.6) for endometrial and the CheckMate-358 study an ORR of 26.3% (95% CI 9.1–51.2) for cervical cancer. With respect to epithelial ovarian cancer (EOC), recent evidence suggests only modest response, as the largest study to date by Matulonis et al. reported in 2019 that pembrolizumab induced an ORR of only 8.0% in 376 patients with EOC. Thus, latest clinical data indicate EOC to be rather “immunologically cold”, most likely due to both an inherently low tumor mutational burden (TMB) and a subsequently limited cellular antigen presentation. As CPI monotherapy therefore seems to be of limited clinical significance, ongoing clinical trials moved to combine CPI with PARP inhibitors and/or with antiangiogenic agents to elucidate possible synergistic antitumoral effects of these combinations. Despite promising preliminary data, the large phase 3 trials are still ongoing. To date, CPI monotherapy in OC remains highly experimental and is only to be administered within clinical studies and a highly selected group of patients.

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