TY - JOUR
T1 - Efficacy and safety of pembrolizumab for patients with previously treated advanced vulvar squamous cell carcinoma
T2 - Results from the phase 2 KEYNOTE-158 study
AU - Shapira-Frommer, Ronnie
AU - Mileshkin, Linda
AU - Manzyuk, Ludmila
AU - Penel, Nicolas
AU - Burge, Matthew
AU - Piha-Paul, Sarina A.
AU - Girda, Eugenia
AU - Lopez Martin, Jose A.
AU - van Dongen, Marloes G.J.
AU - Italiano, Antoine
AU - Xu, Lei
AU - Jin, Fan
AU - Norwood, Kevin
AU - Ott, Patrick A.
N1 - Funding Information:
Funding for this research was provided by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.
Funding Information:
Jose A. Lopez Martin: study funding to the institution from MSD to support study conduct; grants, personal fees, and non-financial support from MSD during the conduct of the study; grants, personal fees, and non-financial support from BMS; grants from Merck-Serono; grants and personal fees from Pfizer; personal fees from Bayer|grants and personal fees from Lilly; grants, personal fees, and non-financial support from PharmaMar; grants, personal fees, and non-financial support from Roche; grants and personal fees from Novartis; and personal fees from Pierre-Fabre; current employee of PharmaMar (beginning after this study was conducted).
Publisher Copyright:
© 2022 The Authors
PY - 2022/8
Y1 - 2022/8
N2 - Objective: Treatment options for advanced vulvar cancer are limited. We evaluated pembrolizumab monotherapy in patients with advanced vulvar squamous cell carcinoma (SCC) enrolled in the phase 2 multicohort, open-label KEYNOTE-158 study (NCT02628067). Methods: Eligible patients had histologically or cytologically documented advanced vulvar SCC with prior treatment failure, measurable disease per RECIST v1.1, ECOG performance status 0–1, and a tumor sample available for biomarker analysis. Pembrolizumab 200 mg was administered intravenously Q3W for up to 35 cycles (approximately 2 years). The primary endpoint was objective response rate (ORR) per RECIST v1.1 by independent central radiologic review in all patients and subgroups based on PD-L1 combined positive score (≥1 [PD-L1–positive] versus <1 [PD-L1–negative]). Results: 101 patients were enrolled. Median time from first dose to data cutoff was 36.0 months. The ORR (95% CI) was 10.9% (5.6%–18.7%) among all patients, 9.5% (4.2%–17.9%) among the 84 patients with PD-L1–positive tumors, and 28.6% (3.7%–71.0%) among the 7 patients with PD-L1–negative tumors. Among patients with a response, median DOR was 20.4 (range, 2.1+ to 28.0) months. Median (95% CI) PFS and OS were 2.1 (2.0–2.1) and 6.2 (4.9–9.4) months, respectively. Treatment-related AEs occurred in 50.5% of patients (grade 3–5, 11.9%) and led to discontinuation of treatment in 5.0% of patients. Two deaths were considered treatment-related (hepatitis, n = 2). Conclusions: Pembrolizumab monotherapy was associated with durable responses in a subset of patients with vulvar SCC. Responses occurred regardless of tumor PD-L1 status. No new safety signals emerged; overall, pembrolizumab was well tolerated.
AB - Objective: Treatment options for advanced vulvar cancer are limited. We evaluated pembrolizumab monotherapy in patients with advanced vulvar squamous cell carcinoma (SCC) enrolled in the phase 2 multicohort, open-label KEYNOTE-158 study (NCT02628067). Methods: Eligible patients had histologically or cytologically documented advanced vulvar SCC with prior treatment failure, measurable disease per RECIST v1.1, ECOG performance status 0–1, and a tumor sample available for biomarker analysis. Pembrolizumab 200 mg was administered intravenously Q3W for up to 35 cycles (approximately 2 years). The primary endpoint was objective response rate (ORR) per RECIST v1.1 by independent central radiologic review in all patients and subgroups based on PD-L1 combined positive score (≥1 [PD-L1–positive] versus <1 [PD-L1–negative]). Results: 101 patients were enrolled. Median time from first dose to data cutoff was 36.0 months. The ORR (95% CI) was 10.9% (5.6%–18.7%) among all patients, 9.5% (4.2%–17.9%) among the 84 patients with PD-L1–positive tumors, and 28.6% (3.7%–71.0%) among the 7 patients with PD-L1–negative tumors. Among patients with a response, median DOR was 20.4 (range, 2.1+ to 28.0) months. Median (95% CI) PFS and OS were 2.1 (2.0–2.1) and 6.2 (4.9–9.4) months, respectively. Treatment-related AEs occurred in 50.5% of patients (grade 3–5, 11.9%) and led to discontinuation of treatment in 5.0% of patients. Two deaths were considered treatment-related (hepatitis, n = 2). Conclusions: Pembrolizumab monotherapy was associated with durable responses in a subset of patients with vulvar SCC. Responses occurred regardless of tumor PD-L1 status. No new safety signals emerged; overall, pembrolizumab was well tolerated.
KW - KEYNOTE-158
KW - Monotherapy
KW - Pembrolizumab
KW - Vulvar cancer
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U2 - 10.1016/j.ygyno.2022.01.029
DO - 10.1016/j.ygyno.2022.01.029
M3 - Article
C2 - 35361487
AN - SCOPUS:85127314983
SN - 0090-8258
VL - 166
SP - 211
EP - 218
JO - Gynecologic oncology
JF - Gynecologic oncology
IS - 2
ER -