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 II KEYNOTE-100 study.
Annals of Oncology
, 30
(7)
pp. 1080-1087.
10.1093/annonc/mdz135.
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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 II KEYNOTE-100 study |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1093/annonc/mdz135 |
| Publisher version: | https://doi.org/10.1093/annonc/mdz135 |
| Language: | English |
| Additional information: | © 2019 THE AUTHORS. Published by Elsevier Ltd. Under a Creative Commons license (https://creativecommons.org/licenses/by-nc-nd/4.0/). |
| Keywords: | ovarian cancer, pembrolizumab, immunotherapy, combined positive score |
| UCL classification: | UCL 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 |
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