Pembrolizumab in patients with programmed death ligand 1–positive advanced ovarian cancer: Analysis of KEYNOTE-028

Andrea Varga, Sarina Piha-Paul, Patrick A. Ott, Janice M. Mehnert, Dominique Berton-Rigaud, Anne Morosky, Ping Yang, Jane Ruman, Daniela Matei

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Objective: To evaluate safety, tolerability, and antitumor activity of pembrolizumab monotherapy in patients with programmed death ligand 1 (PD-L1)–expressing advanced ovarian cancer enrolled in the multicohort, phase Ib KEYNOTE-028 trial. Methods: Key inclusion criteria were age ≥18 years; advanced ovarian epithelial, fallopian tube, or primary peritoneal carcinoma; failure of previous therapy; and tumor PD-L1 positivity. Patients received pembrolizumab (10 mg/kg every 2 weeks) for ≤24 months or until disease progression/intolerable toxicity. Tumor response was assessed per RECIST v1.1 (investigator review). Adverse events (AEs) were graded using CTCAE version 4.0. Primary end point was confirmed objective response rate (ORR) per RECIST v1.1 (investigator review); data cutoff date was February 20, 2017. Results: Twenty-six patients (median age, 57.5 years) with PD-L1–positive advanced metastatic ovarian cancer received pembrolizumab; 38.5% had metastatic disease, and 73.1% previously received ≥3 lines of therapy. Treatment-related AEs (TRAEs) occurred in 19 (73.1%) patients, most commonly arthralgia (19.2%), nausea (15.4%), and pruritus (15.4%). One grade 3 TRAE (increased plasma transaminase level) occurred. No deaths and no treatment discontinuations due to TRAEs occurred. After a median follow-up duration of 15.4 months, ORR was 11.5% (1 complete response, 2 partial responses); 7 patients (26.9%) achieved stable disease. Median progression-free and overall survival were 1.9 (95% CI, 1.8–3.5) and 13.8 (95% CI, 6.7–18.8) months, respectively. Conclusion: Pembrolizumab conferred durable antitumor activity with manageable safety and toxicity in patients with advanced PD-L1–positive ovarian cancer and is under further investigation in an ongoing phase II trial, KEYNOTE-100.

Original languageEnglish (US)
JournalGynecologic Oncology
DOIs
StateAccepted/In press - Jan 1 2018
Externally publishedYes

Fingerprint

Ovarian Neoplasms
Ligands
Therapeutics
Research Personnel
Safety
Fallopian Tubes
Arthralgia
Pruritus
Transaminases
Nausea
Disease-Free Survival
Disease Progression
pembrolizumab
Neoplasms
Carcinoma
Response Evaluation Criteria in Solid Tumors

Keywords

  • Clinical trials
  • Gynecologic cancers
  • Immunotherapy
  • PD-1
  • Pembrolizumab

ASJC Scopus subject areas

  • Oncology
  • Obstetrics and Gynecology

Cite this

Pembrolizumab in patients with programmed death ligand 1–positive advanced ovarian cancer : Analysis of KEYNOTE-028. / Varga, Andrea; Piha-Paul, Sarina; Ott, Patrick A.; Mehnert, Janice M.; Berton-Rigaud, Dominique; Morosky, Anne; Yang, Ping; Ruman, Jane; Matei, Daniela.

In: Gynecologic Oncology, 01.01.2018.

Research output: Contribution to journalArticle

Varga, Andrea ; Piha-Paul, Sarina ; Ott, Patrick A. ; Mehnert, Janice M. ; Berton-Rigaud, Dominique ; Morosky, Anne ; Yang, Ping ; Ruman, Jane ; Matei, Daniela. / Pembrolizumab in patients with programmed death ligand 1–positive advanced ovarian cancer : Analysis of KEYNOTE-028. In: Gynecologic Oncology. 2018.
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abstract = "Objective: To evaluate safety, tolerability, and antitumor activity of pembrolizumab monotherapy in patients with programmed death ligand 1 (PD-L1)–expressing advanced ovarian cancer enrolled in the multicohort, phase Ib KEYNOTE-028 trial. Methods: Key inclusion criteria were age ≥18 years; advanced ovarian epithelial, fallopian tube, or primary peritoneal carcinoma; failure of previous therapy; and tumor PD-L1 positivity. Patients received pembrolizumab (10 mg/kg every 2 weeks) for ≤24 months or until disease progression/intolerable toxicity. Tumor response was assessed per RECIST v1.1 (investigator review). Adverse events (AEs) were graded using CTCAE version 4.0. Primary end point was confirmed objective response rate (ORR) per RECIST v1.1 (investigator review); data cutoff date was February 20, 2017. Results: Twenty-six patients (median age, 57.5 years) with PD-L1–positive advanced metastatic ovarian cancer received pembrolizumab; 38.5{\%} had metastatic disease, and 73.1{\%} previously received ≥3 lines of therapy. Treatment-related AEs (TRAEs) occurred in 19 (73.1{\%}) patients, most commonly arthralgia (19.2{\%}), nausea (15.4{\%}), and pruritus (15.4{\%}). One grade 3 TRAE (increased plasma transaminase level) occurred. No deaths and no treatment discontinuations due to TRAEs occurred. After a median follow-up duration of 15.4 months, ORR was 11.5{\%} (1 complete response, 2 partial responses); 7 patients (26.9{\%}) achieved stable disease. Median progression-free and overall survival were 1.9 (95{\%} CI, 1.8–3.5) and 13.8 (95{\%} CI, 6.7–18.8) months, respectively. Conclusion: Pembrolizumab conferred durable antitumor activity with manageable safety and toxicity in patients with advanced PD-L1–positive ovarian cancer and is under further investigation in an ongoing phase II trial, KEYNOTE-100.",
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T2 - Analysis of KEYNOTE-028

AU - Varga, Andrea

AU - Piha-Paul, Sarina

AU - Ott, Patrick A.

AU - Mehnert, Janice M.

AU - Berton-Rigaud, Dominique

AU - Morosky, Anne

AU - Yang, Ping

AU - Ruman, Jane

AU - Matei, Daniela

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N2 - Objective: To evaluate safety, tolerability, and antitumor activity of pembrolizumab monotherapy in patients with programmed death ligand 1 (PD-L1)–expressing advanced ovarian cancer enrolled in the multicohort, phase Ib KEYNOTE-028 trial. Methods: Key inclusion criteria were age ≥18 years; advanced ovarian epithelial, fallopian tube, or primary peritoneal carcinoma; failure of previous therapy; and tumor PD-L1 positivity. Patients received pembrolizumab (10 mg/kg every 2 weeks) for ≤24 months or until disease progression/intolerable toxicity. Tumor response was assessed per RECIST v1.1 (investigator review). Adverse events (AEs) were graded using CTCAE version 4.0. Primary end point was confirmed objective response rate (ORR) per RECIST v1.1 (investigator review); data cutoff date was February 20, 2017. Results: Twenty-six patients (median age, 57.5 years) with PD-L1–positive advanced metastatic ovarian cancer received pembrolizumab; 38.5% had metastatic disease, and 73.1% previously received ≥3 lines of therapy. Treatment-related AEs (TRAEs) occurred in 19 (73.1%) patients, most commonly arthralgia (19.2%), nausea (15.4%), and pruritus (15.4%). One grade 3 TRAE (increased plasma transaminase level) occurred. No deaths and no treatment discontinuations due to TRAEs occurred. After a median follow-up duration of 15.4 months, ORR was 11.5% (1 complete response, 2 partial responses); 7 patients (26.9%) achieved stable disease. Median progression-free and overall survival were 1.9 (95% CI, 1.8–3.5) and 13.8 (95% CI, 6.7–18.8) months, respectively. Conclusion: Pembrolizumab conferred durable antitumor activity with manageable safety and toxicity in patients with advanced PD-L1–positive ovarian cancer and is under further investigation in an ongoing phase II trial, KEYNOTE-100.

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