Andrea Varga1, Sarina Piha-Paul2, Patrick A Ott3, Janice M Mehnert4, Dominique Berton-Rigaud5, Anne Morosky6, Ping Yang7, Jane Ruman6, Daniela Matei8. 1. Department of Drug Development, Gustave Roussy Cancer Campus, Villejuif, France. Electronic address: Andrea.VARGA@gustaveroussy.fr. 2. Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. 3. Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. 4. Developmental Therapeutics/Phase I Program, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA. 5. Service de Cancérologie médicale, ICO Centre René Gauducheau, Saint-Herblain, France. 6. Department of Oncology, Merck & Co., Inc., Kenilworth, NJ, USA. 7. Biostatistics and Research Decision Sciences, MSD China, Beijing, China. 8. Department of Obstetrics and Gynecology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
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.
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 tumorPD-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.
Authors: Kathryn M Appleton; Ashley K Elrod; Katy A Lassahn; Stephen Shuford; Lillia M Holmes; Teresa M DesRochers Journal: Cancer Immunol Immunother Date: 2021-01-25 Impact factor: 6.968