TY - JOUR
T1 - Pembrolizumab plus chemotherapy in frontline treatment of advanced ovarian cancer
T2 - Clinical and translational results from a phase 2 trial
AU - How, Jeffrey A.
AU - Dang, Minghao
AU - Lee, Sanghoon
AU - Fellman, Bryan
AU - Westin, Shannon N.
AU - Sood, Anil K.
AU - Fleming, Nicole D.
AU - Shafer, Aaron
AU - Yuan, Ying
AU - Liu, Jinsong
AU - Zhao, Li
AU - Celestino, Joseph
AU - Hajek, Richard
AU - Morgan, Margaret B.
AU - Parra, Edwin R.
AU - Laberiano Fernandez, Caddie D.
AU - Arrechedera, Claudio A.
AU - Solis Soto, Luisa Maren
AU - Schmeler, Kathleen M.
AU - Nick, Alpa
AU - Lu, Karen H.
AU - Coleman, Robert
AU - Wang, Linghua
AU - Jazaeri, Amir A.
N1 - Publisher Copyright:
© 2024 Elsevier Inc.
PY - 2025/1/10
Y1 - 2025/1/10
N2 - Background: The efficacy and feasibility of pembrolizumab combined with chemotherapy in frontline management of advanced high-grade epithelial ovarian cancer (EOC) is unknown. Additionally, modification of the tumor microenvironment following neoadjuvant therapy is not well understood. Methods: In this single-arm phase 2 trial (this study was registered at ClinicalTrials.gov: NCT02520154), eligible patients received up to 4 cycles of neoadjuvant chemotherapy followed by interval cytoreduction, 3 cycles of adjuvant intravenous carboplatin/weekly paclitaxel/pembrolizumab, and finally maintenance pembrolizumab until progression or toxicity (maximum 20 cycles). The primary endpoint was progression-free survival (PFS). Secondary endpoints included feasibility, toxicity, and overall survival (OS). PD-L1 staining, multiplex immunofluorescence staining, RNA sequencing, reverse-phase protein array analyses were performed on pre- and post-chemotherapy samples. Findings: Thirty-one eligible patients were enrolled. Median PFS and OS was 14.88 (95% CI 12.39–23.00) and 57.43 months (95% CI 30.88–not reached), respectively. Among those with PD-L1 combined positive score (CPS) ≥10, the median PFS and OS were not reached compared to those with CPS <10 (10.50 and 30.90 months, respectively). Feasibility was met, with all patients completing their planned adjuvant cycles. Treatment discontinuation due to immune-related toxicity occurred in 6 patients (20%). Chemotherapy resulted in an infiltration of anti-tumor immune cells in the tumor microenvironment. Samples of patients with the best PFS demonstrated increased expression of NF-κB, TGF-β, and β-catenin signaling. Conclusions: Pembrolizumab with chemotherapy was feasible and resulted in PFS within the historical range for this EOC population. Patients with CPS ≥10 may benefit more from this regimen, and future studies should investigate this potential biomarker. Funding: This investigator-initiated trial was funded by Merck.
AB - Background: The efficacy and feasibility of pembrolizumab combined with chemotherapy in frontline management of advanced high-grade epithelial ovarian cancer (EOC) is unknown. Additionally, modification of the tumor microenvironment following neoadjuvant therapy is not well understood. Methods: In this single-arm phase 2 trial (this study was registered at ClinicalTrials.gov: NCT02520154), eligible patients received up to 4 cycles of neoadjuvant chemotherapy followed by interval cytoreduction, 3 cycles of adjuvant intravenous carboplatin/weekly paclitaxel/pembrolizumab, and finally maintenance pembrolizumab until progression or toxicity (maximum 20 cycles). The primary endpoint was progression-free survival (PFS). Secondary endpoints included feasibility, toxicity, and overall survival (OS). PD-L1 staining, multiplex immunofluorescence staining, RNA sequencing, reverse-phase protein array analyses were performed on pre- and post-chemotherapy samples. Findings: Thirty-one eligible patients were enrolled. Median PFS and OS was 14.88 (95% CI 12.39–23.00) and 57.43 months (95% CI 30.88–not reached), respectively. Among those with PD-L1 combined positive score (CPS) ≥10, the median PFS and OS were not reached compared to those with CPS <10 (10.50 and 30.90 months, respectively). Feasibility was met, with all patients completing their planned adjuvant cycles. Treatment discontinuation due to immune-related toxicity occurred in 6 patients (20%). Chemotherapy resulted in an infiltration of anti-tumor immune cells in the tumor microenvironment. Samples of patients with the best PFS demonstrated increased expression of NF-κB, TGF-β, and β-catenin signaling. Conclusions: Pembrolizumab with chemotherapy was feasible and resulted in PFS within the historical range for this EOC population. Patients with CPS ≥10 may benefit more from this regimen, and future studies should investigate this potential biomarker. Funding: This investigator-initiated trial was funded by Merck.
KW - Translation to patients
KW - clinical trial
KW - combination chemotherapy
KW - feasibility
KW - immunotherapy
KW - ovarian cancer
KW - pembrolizumab
KW - translational
KW - tumor immune microenvironment
UR - http://www.scopus.com/inward/record.url?scp=85203081318&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85203081318&partnerID=8YFLogxK
U2 - 10.1016/j.medj.2024.07.022
DO - 10.1016/j.medj.2024.07.022
M3 - Article
C2 - 39151421
AN - SCOPUS:85203081318
SN - 2666-6359
VL - 6
JO - Med
JF - Med
IS - 1
M1 - 100494
ER -