Abstract
Purpose: The objective of this study was to assess the efficacy and safety of pembrolizumab in combination with standard carboplatin/paclitaxel in patients with advanced endometrial cancer. Patients and Methods: This single-arm, open-label, multicenter phase II study enrolled patients with RECIST measurable advanced endometrial cancer. Patients could have received ≤ 1 prior platinum-based regimen and ≤ one non-platinum chemotherapy. The primary endpoint was objective response rate (ORR). Planned sample size of 46 subjects provided 80% power to detect 15% ORR improvement compared with historical control rate of 50%. Results: A total of 46 patients were enrolled and 43 were evaluable for ORR. Median age was 66 (range: 43–86). Thirty-four (73.9%) patients had recurrent and 12 (26.1%) primary metastatic endometrial cancer. Patients received carboplatin AUC6, paclitaxel 175 mg/m2, and pembrolizumab 200 mg i.v. every 3 weeks for up to six cycles. ORR was 74.4% (32/43), higher than historic controls (P = 0.001). Median progression-free survival (PFS) was 10.6 months (95% confidence interval, 8.3–13.9 months). The most common grade 1–2 treatment-related adverse event (TRAE) included anemia (56.5%), alopecia (47.8%), fatigue (47.8%), and neuropathy (13%), while the most common grade 3–4 TRAEs were lymphopenia, leukopenia, and anemia (19.6% each). High-dimensional spectral flow cytometry (CyTEK) identified enrichment in peripheral CD8+ and CD4+ T-cell populations at baseline in responders. The CD8+ T-cell compartment in responders exhibited greater expression levels of PD-1 and PD-L1 and higher abundance of effector memory CD8+ cells compared with nonresponders. Conclusions: Addition of pembrolizumab to carboplatin and paclitaxel for advanced endometrial cancer was tolerated and improved ORR compared with historical outcomes. Significance: The results of the study support that the combination of pembrolizumab with carboplatin and paclitaxel is well tolerated and active in patients with advanced endometrial cancer. The duration of response and the PFS were significantly longer in patients with mismatch repair deficient/microsatellite instability-high compared with mismatch repair proficient/microsatellite stable tumors. Responders to treatment tend to have enriched CD8+ T-cell and CD4+ T-cell populations among peripheral blood mononuclear cells at baseline.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1293-1303 |
| Number of pages | 11 |
| Journal | Cancer Research Communications |
| Volume | 2 |
| Issue number | 10 |
| DOIs | |
| State | Published - 2022 |
Funding
This study was approved and funded by the Big Ten Research Consortium with research support provided by Merck. Career development support was provided to Dr Barber by the NICDH (K12 HD050121) and the GOG Foundation. Translational analyses were supported through the Immunotherapy Core and the NCI awards CA208354, CA222963, CA250101 to B. Zhang. We appreciate the support from the Big Ten Research Consortium and the Clinical Trial Office of the Robert H Lurie Comprehensive Cancer Center. We acknowledge contributions from Drs. Shohreh Shahabi, John Lurain, as well as Karen Novak, APN and Nancy Anderson, APN and editorial assistance from Anne Grace, PhD. E.L. Barber reports grants from GOG Foundation during the conduct of the study; grants and personal fees from Merck outside the submitted work. D. Teoh reports other from Tesaro/GSK, Moderna, and Jounce outside the submitted work. J. Schilder reports other from GlaxoSmithKline outside the submitted work. M. Kocherginsky reports grants from NIH/NCI during the conduct of the study; in addition, M. Kocherginsky has a patent to The University of Chicago issued and with royalties paid. D. Matei reports grants, personal fees, and nonfinancial support from Merck and grants from Department of Defense during
ASJC Scopus subject areas
- Oncology
- Cancer Research
