A phase 2 study of pembrolizumab and weekly paclitaxel for platinum-resistant epithelial ovarian cancer.

[OBJECTIVE] Weekly dose-dense paclitaxel may have immunomodulatory effects, enhancing immune responses via cytotoxic T-cell infiltration. Therefore, we assessed the combination of weekly dose-dense paclitaxel with pembrolizumab in patients with platinum-resistant ovarian cancer that persisted or recurred within 6 months of previous platinum chemotherapy.

[METHODS] A multi-center open-label, single-arm study was conducted and participants received weekly intravenous paclitaxel 80 mg/m and every 3-week intravenous pembrolizumab 200 mg until progression or toxicity. The primary objectives were to determine the progression-free survival at 6 months and safety. Secondary analyses included objective response rate, disease control rate, duration of response, median progression-free survival, and overall survival. All patients receiving any drug were included in the toxicity evaluation. Exploratory analysis of programmed cell death ligand 1 in archival tissue was performed.

[RESULTS] Of the 42 patients enrolled, 37 had Response Evaluation Criteria in Solid Tumors (RECIST)-evaluable disease, and 41 were assessable in the intention-to-treat analysis. In the RECIST-evaluable cohort, the progression-free survival at 6 months was 58.6% (95% confidence interval 41.0 to 72.7), the overall response rate was 51.4% (range; 34.4-68.1), disease control rate was 86.5% (range; 75.5-97.5), and the median progression-free survival was 7.23 (range; 4.54-11.00) months. In the intention-to-treat analysis, the progression-free survival at 6 months was 55.3% (range; 38.8-69.1), overall response rate was 46.3% (range; 30.7-62.6), disease control rate was 78.0% (range; 62.4-89.4), and median progression-free survival was 6.87 (range; 4.37-8.9) months. The median duration of response for responders was 8.8 (range; 4.4-13.0) months. The median overall survival for the RECIST-evaluable and intention-to-treat groups were 26.3 (13.4 to not reached) and 25.9 (range; 13.3-27.1) months, respectively. Most common adverse events were anemia (69.1%), fatigue (52.4%), lab abnormalities (50.0%), decreased neutrophils (23.8%), and edema (47.6%).

[CONCLUSIONS] The combination of weekly dose-dense paclitaxel and pembrolizumab demonstrated promising activity and was well tolerated, although edema may be increased.