TY - JOUR
T1 - Safety and antitumor activity of pembrolizumab in advanced programmed death ligand 1–positive endometrial cancer
T2 - Results from the KEYNOTE-028 study
AU - Ott, Patrick A.
AU - Bang, Yung Jue
AU - Berton-Rigaud, Dominique
AU - Elez, Elena
AU - Pishvaian, Michael J.
AU - Rugo, Hope S.
AU - Puzanov, Igor
AU - Mehnert, Janice M.
AU - Aung, Kyaw L.
AU - Lopez, Juanita
AU - Carrigan, Marion
AU - Saraf, Sanatan
AU - Chen, Mei
AU - Soria, Jean Charles
N1 - Funding Information:
Supported by Merck, Kenilworth, NJ. Medical writing and editorial assistance, funded by Merck (Kenilworth, NJ), were provided by Jacqueline Kolston and Matthew Grzywacz of the ApotheCom oncology team (Yardley, PA). We thank the patients and their families and caregivers for participating in this trial. We also thank Robin Mogg, Diane Levitan, and Matthew J. Marton (Merck) for their contributions in the development of this article and Roger Dansey (Merck) for critical manuscript review.
Publisher Copyright:
© 2017 by American Society of Clinical Oncology.
PY - 2017/8/1
Y1 - 2017/8/1
N2 - Purpose: The multicohort phase Ib KEYNOTE-028 (NCT02054806) study was designed to evaluate the safety and efficacy of pembrolizumab, an anti–programmed death 1 monoclonal antibody, in patients with programmed death ligand 1 (PD-L1)–positive advanced solid tumors. The results from the advanced endometrial cancer cohort are reported. Patients and Methods: Female patients with locally advanced or metastatic PD-L1–positive endometrial cancer who had experienced progression after standard therapy were eligible. Patients received pembrolizumab 10 mg/kg every 2 weeks for up to 24 months or until progression or unacceptable toxicity. Primary efficacy end point was objective response rate by RECIST (version 1.1). Secondary end points included safety, duration of response (DOR), progression-free survival, and overall survival. The data cutoff was February 17, 2016. Results: Of 75 patients screened, 36 (48.0%) had PD-L1–positive tumors, and 24 (32.0%) were enrolled. Fifteen (62.5%) of these 24 patients had received at least two previous lines of therapy for advanced disease. Three patients (13.0%) achieved confirmed partial response (95% CI, 2.8% to 33.6%); the median DOR was not reached. Two patients were still receiving treatment and exhibiting continued response at time of data cutoff. Three additional patients (13.0%) achieved stable disease, with a median duration of 24.6 weeks. One patient who achieved partial response had a polymerase E mutation. Thirteen patients (54.2%) experienced treatment-related adverse events (AEs), with fatigue (20.8%), pruritus (16.7%), pyrexia (12.5%), and decreased appetite (12.5%) occurring in ≥ 10% of patients. Grade 3 treatment-related AEs were reported in four patients. No patient experienced a grade 4 AE, and no patient discontinued treatment because of an AE. Conclusion: Pembrolizumab demonstrated a favorable safety profile and durable antitumor activity in a subgroup of patients with heavily pretreated advanced PD-L1–positive endometrial cancer.
AB - Purpose: The multicohort phase Ib KEYNOTE-028 (NCT02054806) study was designed to evaluate the safety and efficacy of pembrolizumab, an anti–programmed death 1 monoclonal antibody, in patients with programmed death ligand 1 (PD-L1)–positive advanced solid tumors. The results from the advanced endometrial cancer cohort are reported. Patients and Methods: Female patients with locally advanced or metastatic PD-L1–positive endometrial cancer who had experienced progression after standard therapy were eligible. Patients received pembrolizumab 10 mg/kg every 2 weeks for up to 24 months or until progression or unacceptable toxicity. Primary efficacy end point was objective response rate by RECIST (version 1.1). Secondary end points included safety, duration of response (DOR), progression-free survival, and overall survival. The data cutoff was February 17, 2016. Results: Of 75 patients screened, 36 (48.0%) had PD-L1–positive tumors, and 24 (32.0%) were enrolled. Fifteen (62.5%) of these 24 patients had received at least two previous lines of therapy for advanced disease. Three patients (13.0%) achieved confirmed partial response (95% CI, 2.8% to 33.6%); the median DOR was not reached. Two patients were still receiving treatment and exhibiting continued response at time of data cutoff. Three additional patients (13.0%) achieved stable disease, with a median duration of 24.6 weeks. One patient who achieved partial response had a polymerase E mutation. Thirteen patients (54.2%) experienced treatment-related adverse events (AEs), with fatigue (20.8%), pruritus (16.7%), pyrexia (12.5%), and decreased appetite (12.5%) occurring in ≥ 10% of patients. Grade 3 treatment-related AEs were reported in four patients. No patient experienced a grade 4 AE, and no patient discontinued treatment because of an AE. Conclusion: Pembrolizumab demonstrated a favorable safety profile and durable antitumor activity in a subgroup of patients with heavily pretreated advanced PD-L1–positive endometrial cancer.
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U2 - 10.1200/JCO.2017.72.5952
DO - 10.1200/JCO.2017.72.5952
M3 - Article
C2 - 28489510
AN - SCOPUS:85026732536
SN - 0732-183X
VL - 35
SP - 2535
EP - 2541
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 22
ER -