Journal article
Clinical and Biological Activity of Chemoimmunotherapy in Advanced Endometrial Adenocarcinoma: A Phase II Trial of the Big Ten Cancer Research Consortium
Cancer research communications, Vol.2(10), pp.1293-1303
10/01/2022
DOI: 10.1158/2767-9764.crc-22-0147
PMCID: PMC9648489
PMID: 36388466
Abstract
PurposeThe 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 (EC). Patients and MethodsThis single-arm, open-label, multi-center phase II study enrolled patients with RECIST measurable advanced EC. 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 to historical control rate of 50%. Results46 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 EC. Patients received carboplatin AUC 6, paclitaxel 175mg/m2 and pembrolizumab 200mg IV every 3 weeks for up to 6 cycles. ORR was 74.4% (32/43), higher than historic controls (p = 0.001). Median PFS was 10.6 months (95% CI 8.3-13.9 months). The most common grade 1-2 treatment related adverse event (TRAEs) 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 to non-responders. ConclusionsAddition of pembrolizumab to carboplatin and paclitaxel for advanced EC was tolerated and improved ORR compared to historical outcomes.
Details
- Title: Subtitle
- Clinical and Biological Activity of Chemoimmunotherapy in Advanced Endometrial Adenocarcinoma: A Phase II Trial of the Big Ten Cancer Research Consortium
- Creators
- Emma Longley Barber - Northwestern UniversitySiqi Chen - Northwestern UniversityMario Javier Pineda - Ironwood Cancer and Research Centers, Gilbert, AZ, United StatesSharon E Robertson - Indiana University BloomingtonEmily K Hill - University of IowaDeanna Teoh - University of MinnesotaJeanne Schilder - Indiana UniversityKaitlyn L O'SheaMasha Kocherginsky - Northwestern UniversityBin Zhang - Northwestern UniversityDaniela Matei - Northwestern University
- Resource Type
- Journal article
- Publication Details
- Cancer research communications, Vol.2(10), pp.1293-1303
- DOI
- 10.1158/2767-9764.crc-22-0147
- PMID
- 36388466
- PMCID
- PMC9648489
- NLM abbreviation
- Cancer Res Commun
- eISSN
- 2767-9764
- Grant note
- name: HHS | National Institutes of Health, award: K12 HD050121; name: HHS | NIH | National Cancer Institute, award: CA208354; name: HHS | NIH | National Cancer Institute, award: CA222963; name: HHS | NIH | National Cancer Institute, award: CA250101; name: Big Ten Research Consortium; DOI: 10.13039/100018096, name: GOG Foundation
- Language
- English
- Date published
- 10/01/2022
- Academic Unit
- Obstetrics and Gynecology
- Record Identifier
- 9984317111202771
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