Is Adding Entinostat to Avelumab of Benefit in Treating Advanced Epithelial Ovarian Cancer?
Posted: Monday, August 12, 2019
Adding the histone deacetylase inhibitor entinostat to the anti–PD-L1 monoclonal antibody avelumab does not seem to prolong median progression-free survival compared with avelumab alone in patients with heavily pretreated advanced epithelial ovarian cancer. The combination of drugs also resulted in greater toxicity, according to Karen Anne Cadoo, MD, of Memorial Sloan Kettering Cancer Center in New York, and colleagues, who presented the phase II trial data at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago (Abstract 5511) and published their findings in the Journal of Clinical Oncology.
The study enrolled patients with epithelial ovarian cancer who had either experienced disease progression or recurrence after first line platinum-based chemotherapy and had received three to six prior lines of therapy. A total of 126 patients were randomly assigned to receive either avelumab (10 mg/kg) plus entinostat (5 mg) or avelumab plus a placebo. Of these patients, 83% had serous histology.
The median progression-free survival was 1.64 months for patients treated with the combination therapy compared with 1.51 months for those treated with avelumab alone (P = .31, hazard ratio = 0.90). There were no significant differences in overall response rate (6% vs. 5%) or overall survival (not evaluated vs. 11.3 months). In the four patients with clear cell ovarian cancer, no responses were observed.
The incidence of any-grade adverse events was higher in the entinostat arm than in the arm with avelumab alone (93% vs. 78%), and there were more grade 3 or 4 adverse events in the combination arm (41% vs. 10%). The most common adverse events with entinostat and avelumab of any grade were fatigue (46%), nausea (31%), diarrhea (26%), anemia (26%), and chills (20%). Of the patients in the entinostat arm, 47% required dose holds or reductions. Discontinuation of therapy due to adverse events and the duration of therapy were similar between the two arms.
Disclosure: The study authors’ disclosure information may be found at coi.asco.org.