UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

Antitumor Activity and Safety of Pembrolizumab in Patients with Advanced Recurrent Ovarian Cancer: Results from the Phase 2 KEYNOTE-100 Study

Matulonis, UA; Shapira-Frommer, R; Santin, AD; Lisyanskaya, AS; Pignata, S; Vergote, I; Raspagliesi, F; ... Ledermann, JA; + view all (2019) Antitumor Activity and Safety of Pembrolizumab in Patients with Advanced Recurrent Ovarian Cancer: Results from the Phase 2 KEYNOTE-100 Study. Annals of Oncology 10.1093/annonc/mdz135. (In press).

[img] Text
Ledermann_Antitumor Activity and Safety of Pembrolizumab in Patients with Advanced Recurrent Ovarian Cancer_AAM.pdf - Accepted version
Access restricted to UCL open access staff until 3 May 2020.

Download (922kB)

Abstract

BACKGROUND: Advanced recurrent ovarian cancer (ROC) is the leading cause of gynecologic cancer-related death in developed countries and new treatments are needed. Previous studies of immune checkpoint blockade showed low objective response rates (ORR) in ROC with no identified predictive biomarker. PATIENTS AND METHODS: This phase 2 study of pembrolizumab (NCT02674061) examined 2 patient cohorts with ROC: cohort A received 1-3 prior lines of treatment with a platinum-free (PFI) or treatment-free interval (TFI) between 3-12 months and cohort B received 4-6 prior lines with a PFI/TFI of ≥ 3 months. Pembrolizumab 200 mg was administered intravenously every 3 weeks until cancer progression, toxicity, or completion of 2 years. Primary endpoints were ORR by Response Evaluation Criteria in Solid Tumors version 1.1 per blinded independent central review by cohort and by PD-L1 expression measured as combined positive score (CPS). Secondary endpoints included duration of response (DOR), disease control rate (DCR), progression free survival (PFS), overall survival (OS), and safety. RESULTS: Cohort A enrolled 285 patients; the first 100 served as the training set for PD-L1 biomarker analysis. Cohort B enrolled 91 patients. ORR was 7.4% for cohort A and 9.9% for cohort B. Median DOR was 8.2 months for cohort A and not reached for cohort B. DCR was 37.2% and 37.4%, respectively, in cohorts A and B. Based on the training set analysis, CPS 1 and 10 were selected for evaluation in the confirmation set. In the confirmation set, ORR was 4.1% for CPS<1, 5.7% CPS ≥1, and 10.0% for CPS ≥10. PFS was 2.1 months for both cohorts. Median OS was not reached for cohort A and was 17.6 months for cohort B. Toxicities were consistent with other single-agent pembrolizumab trials. CONCLUSIONS: Single-agent pembrolizumab showed modest activity in patients with ROC. Higher PD-L1 expression was correlated with higher response. CLINICAL TRIAL NUMBER: Clinicaltrials.gov, NCT02674061.

Type: Article
Title: Antitumor Activity and Safety of Pembrolizumab in Patients with Advanced Recurrent Ovarian Cancer: Results from the Phase 2 KEYNOTE-100 Study
Location: England
DOI: 10.1093/annonc/mdz135
Publisher version: https://doi.org/10.1093/annonc/mdz135
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: ovarian cancer, pembrolizumab, immunotherapy, combined positive score
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > CRUK Cancer Trials Centre
URI: https://discovery.ucl.ac.uk/id/eprint/10074272
Downloads since deposit
2Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item