A R Hansen1, C Massard2, P A Ott3, N B Haas4, J S Lopez5, S Ejadi6, J M Wallmark7, B Keam8, J-P Delord9, R Aggarwal10, M Gould11, P Yang11, S M Keefe11, S A Piha-Paul12. 1. Division of Medical Oncology, UHN Princess Margaret Cancer Centre, Toronto, Ontario, Canada. Electronic address: aaron.hansen@uhn.ca. 2. Department of Medical Oncology, Gustave Roussy, Villejuif, France. 3. Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, USA. 4. Division of Hematology Oncology, Hospital of the University of Pennsylvania, Philadelphia, USA. 5. The Royal Marsden and the Institute of Cancer Research, London, UK. 6. Department of Medical Oncology, Virginia G. Piper Cancer Center at HonorHealth, Scottsdale, USA. 7. Department of Medical Oncology, Associates in Oncology & Hematology, Rockville, USA. 8. Department of HematoOncology, Seoul National University Hospital, Seoul, Republic of Korea. 9. Department of Medical Oncology, Institut Claudius Regaud, Toulouse, France. 10. Department of Medicine, Division of Hematology/Oncology, UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, USA. 11. Department of Oncology, Merck & Co., Inc, Kenilworth, USA. 12. Department of Investigational Clinical Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, USA.
Abstract
Background: Patients with castration-resistant prostate cancer derive only modest clinical benefit from available therapies. Blockade of the inhibitory programmed death 1 (PD-1) receptor by monoclonal antibodies has been effective in several malignancies. Results from the prostate adenocarcinoma cohort of the nonrandomized phase Ib KEYNOTE-028 trial of pembrolizumab in advanced solid tumors are presented. Materials and methods: Key eligibility criteria included advanced prostate adenocarcinoma, unsuccessful standard therapy, measurable disease per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1), and PD-1 ligand (PD-L1) expression in ≥1% of tumor or stromal cells. Patients received pembrolizumab 10 mg/kg every 2 weeks until disease progression or intolerable toxicity for up to 24 months. Primary end point was objective response rate (ORR) per RECIST v1.1 by investigator review. Results: Median patient age in this cohort (n = 23) was 65 years; 73.9% of patients received at least two prior therapies for metastatic disease. There were four confirmed partial responses, for an ORR of 17.4% [95% confidence interval (CI) 5.0%-38.8%]; 8 of 23 (34.8%) patients had stable disease. Median duration of response was 13.5 months. Median progression-free survival (PFS) and overall survival (OS) were 3.5 and 7.9 months, respectively; 6-month PFS and OS rates were 34.8% and 73.4%, respectively. One patient remained on treatment at data cutoff. After a median follow-up of 7.9 months, 14 (60.9%) patients experienced treatment-related adverse events (TRAEs), most commonly nausea (n = 3, 13.0%). Four (17.3%) experienced grade 3/4 TRAEs: grade 3 peripheral neuropathy, grade 3 asthenia, grade 3 fatigue, and grade 4 lipase increase. No pembrolizumab-related deaths or discontinuations occurred. Conclusion: Pembrolizumab resulted in durable objective response in a subset of patients with heavily pretreated, advanced PD-L1-positive prostate cancer, and its side effect profile was favorable. ClinicalTrials.gov Identifier: NCT02054806.
Background: Patients with castration-resistant prostate cancer derive only modest clinical benefit from available therapies. Blockade of the inhibitory programmed death 1 (PD-1) receptor by monoclonal antibodies has been effective in several malignancies. Results from the prostate adenocarcinoma cohort of the nonrandomized phase Ib KEYNOTE-028 trial of pembrolizumab in advanced solid tumors are presented. Materials and methods: Key eligibility criteria included advanced prostate adenocarcinoma, unsuccessful standard therapy, measurable disease per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1), and PD-1 ligand (PD-L1) expression in ≥1% of tumor or stromal cells. Patients received pembrolizumab 10 mg/kg every 2 weeks until disease progression or intolerable toxicity for up to 24 months. Primary end point was objective response rate (ORR) per RECIST v1.1 by investigator review. Results: Median patient age in this cohort (n = 23) was 65 years; 73.9% of patients received at least two prior therapies for metastatic disease. There were four confirmed partial responses, for an ORR of 17.4% [95% confidence interval (CI) 5.0%-38.8%]; 8 of 23 (34.8%) patients had stable disease. Median duration of response was 13.5 months. Median progression-free survival (PFS) and overall survival (OS) were 3.5 and 7.9 months, respectively; 6-month PFS and OS rates were 34.8% and 73.4%, respectively. One patient remained on treatment at data cutoff. After a median follow-up of 7.9 months, 14 (60.9%) patients experienced treatment-related adverse events (TRAEs), most commonly nausea (n = 3, 13.0%). Four (17.3%) experienced grade 3/4 TRAEs: grade 3 peripheral neuropathy, grade 3 asthenia, grade 3 fatigue, and grade 4 lipase increase. No pembrolizumab-related deaths or discontinuations occurred. Conclusion:Pembrolizumab resulted in durable objective response in a subset of patients with heavily pretreated, advanced PD-L1-positive prostate cancer, and its side effect profile was favorable. ClinicalTrials.gov Identifier: NCT02054806.
Authors: Emmanuel S Antonarakis; Josep M Piulats; Marine Gross-Goupil; Jeffrey Goh; Kristiina Ojamaa; Christopher J Hoimes; Ulka Vaishampayan; Ranaan Berger; Ahmet Sezer; Tuomo Alanko; Ronald de Wit; Chunde Li; Aurelius Omlin; Giuseppe Procopio; Satoshi Fukasawa; Ken-Ichi Tabata; Se Hoon Park; Susan Feyerabend; Charles G Drake; Haiyan Wu; Ping Qiu; Jeri Kim; Christian Poehlein; Johann Sebastian de Bono Journal: J Clin Oncol Date: 2019-11-27 Impact factor: 44.544
Authors: Jason M Redman; Logan P Rhea; Lisa Cordes; Helen Owens; Ravi A Madan; Marijo Bilusic; James L Gulley; Jung-Min Lee; William L Dahut; Fatima Karzai Journal: Clin Genitourin Cancer Date: 2019-02-14 Impact factor: 2.872