Antitumor activity and safety of pembrolizumab in patients with advanced recurrent ovarian cancer: results from the phase II KEYNOTE-100 study |
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| Institution: | 1. Division of Gynecologic Oncology, Dana-Farber Cancer Institute, Boston, USA;2. Oncology Institute and Ella Lemelbaum Institute for Immuno-Oncology, Sheba Medical Center, Ramat Gan, Israel;3. Obstetrics, Gynecology & Reproductive Sciences, Yale University School of Medicine, New Haven, USA;4. Department of Gynaecological Oncology, City Clinical Oncology Dispensary, Saint Petersburg, Russia;5. Department of Urogynaecological Oncology, Istituto Nazionale per lo Studio e la Cura dei Tumori “Fondazione G Pascale”, IRCCS, Naples, Italy;6. Department of Obstetrics and Gynaecology and Gynaecologic Oncology, University Hospital Leuven, Leuven, Belgium;7. Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy;8. Department of Medical Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands;9. Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, USA;10. Hôpital Notre-Dame - Pavillon L-C Simard, Centre Hospitalier de L’Université de Montréal (CHUM), Montreal, Canada;11. Gynecology and Obstetrics, Charité-Medical University of Berlin, Berlin, Germany;12. Department of Surgical Sciences, University of Milano-Bicocca and European Institute of Oncology, Milano, Italy;13. Medical Oncology, Clinica Universidad de Navarra; formerly of MD Anderson International España, Madrid;14. Vall d’Hebron University Hospital, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain;15. Medical Oncology, Radboud University Medical Center, Nijmegen, The Netherlands;16. Clinic of Obstetrics and Gynecology, Vilnius University Institute of Clinical Medicine, Vilnius, Lithuania;17. Companion Diagnostics, Merck & Co., Inc, Kenilworth, USA;18. BARDS, MSD China, Beijing, China;19. Clinical Development, Merck & Co., Inc., Kenilworth, USA;20. UCL Cancer Institute and UCL Hospitals, Department of Oncology, University College London, London, UK |
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| Abstract: | BackgroundAdvanced 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 methodsThis phase II study of pembrolizumab (NCT02674061) examined two patient cohorts with ROC: cohort A received one to three prior lines of treatment with a platinum-free interval (PFI) or treatment-free interval (TFI) between 3 and 12 months and cohort B received four to six 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 end points 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 end points included duration of response (DOR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety.ResultsCohort 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.ConclusionsSingle-agent pembrolizumab showed modest activity in patients with ROC. Higher PD-L1 expression was correlated with higher response.Clinical Trial NumberClinicaltrials.gov, NCT02674061 |
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