Hyun Cheol Chung1, Sarina A Piha-Paul2, Jose Lopez-Martin3, Jan H M Schellens4, Steven Kao5, Wilson H Miller6, Jean-Pierre Delord7, Bo Gao8, David Planchard9, Maya Gottfried10, Alona Zer11, Shadia I Jalal12, Nicolas Penel13, Janice M Mehnert14, Ignacio Matos15, Jaafar Bennouna16, Dong-Wan Kim17, Lei Xu18, Suba Krishnan18, Kevin Norwood18, Patrick A Ott19. 1. Department of Medical Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea. Electronic address: unchung8@yuhs.ac. 2. Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas. 3. Department of Medical Oncology, 12 de Octubre University Hospital and Research Institute (i+12), Madrid, Spain. 4. Division of Pharmacology, Netherlands Cancer Institute, Amsterdam, Netherlands. 5. Medical Oncology, Chris O'Brien Lifehouse, Camperdown, New South Wales, Australia. 6. Segal Cancer Centre, Jewish General Hospital, Montreal, Quebec, Canada; Rossy Cancer Network, Montreal, Quebec, Canada; Department of Medicine, McGill University, Montreal, Quebec, Canada. 7. Department of Oncology, Institut Claudius Regaud Institut Universitaire du Cancer-Oncopole, Toulouse, France. 8. Blacktown Hospital, Western Sydney Local Health District, Blacktown, New South Wales, Australia. 9. Department of Medical Oncology, Thoracic Group, Gustave Roussy, Villejuif, France. 10. Oncology, Meir Medical Center, Kfar Saba, Israel. 11. Davidoff Cancer Center, Rabin Medical Center, Petah Tikva, Israel. 12. Indiana University, Simon Cancer Center, Indianapolis, Indiana. 13. Department of Medical Oncology, Centre Oscar Lambret, Lille, France. 14. Developmental Therapeutics, Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey. 15. Department of Medical Oncology, Vall d'Hebron Institute of Oncology, Barcelona, Spain. 16. Institut de Cancérologie de l'Ouest, Nantes, France. 17. Seoul National University Hospital College of Medicine, Seoul, South Korea. 18. Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, New Jersey. 19. Dana-Farber Cancer Institute, Boston, Massachusetts.
Abstract
INTRODUCTION: Pembrolizumab has shown clinical benefit in patients with previously treated recurrent or metastatic SCLC in the phase 1b multicohort study KEYNOTE-028 (NCT02054806) and the phase 2 multicohort study KEYNOTE-158 (NCT02628067). We present a pooled analysis of patients from KEYNOTE-028 and KEYNOTE-158 who had received two or more lines of previous therapy for SCLC. METHODS: Eligible patients were aged 18 years and above, had histologically or cytologically confirmed incurable recurrent or metastatic SCLC, had an Eastern Cooperative Oncology Group performance status of 1 and below, and had received two or more lines of previous therapy. Patients in KEYNOTE-028 were required to have a programmed death ligand 1 (PD-L1)-positive tumor. Patients received pembrolizumab (10 mg/kg every 2 weeks in KEYNOTE-028 or 200 mg every 3 weeks in KEYNOTE-158) for up to 2 years. The primary end point was objective response rate per Response Evaluation Criteria in Solid Tumors version 1.1, which is presented here per independent review. RESULTS: Eighty-three patients who had received two or more lines of previous therapy (KEYNOTE-028, n = 19; KEYNOTE-158, n = 64) were included. Median follow-up duration was 7.7 (range, 0.5-48.7) months. Objective response rate was 19.3% (95% confidence interval: 11.4-29.4); two patients had complete response (one with a PD-L1-positive tumor), and 14 patients had partial response (13 with PD-L1-positive tumors). The median duration of response was not reached (range, 4.1‒35.8+ mo; plus sign indicates ongoing response); 61% of responders had responses lasting 18 months or longer. Fifty-one patients (61.4%) experienced any-grade treatment-related adverse events; eight patients (9.6%) had grade 3 or higher events. CONCLUSIONS: Pembrolizumab exhibited durable antitumor activity in a subset of patients with recurrent or metastatic SCLC who had undergone two or more previous lines of therapy, regardless of PD-L1 expression. Pembrolizumab was well tolerated.
INTRODUCTION:Pembrolizumab has shown clinical benefit in patients with previously treated recurrent or metastatic SCLC in the phase 1b multicohort study KEYNOTE-028 (NCT02054806) and the phase 2 multicohort study KEYNOTE-158 (NCT02628067). We present a pooled analysis of patients from KEYNOTE-028 and KEYNOTE-158 who had received two or more lines of previous therapy for SCLC. METHODS: Eligible patients were aged 18 years and above, had histologically or cytologically confirmed incurable recurrent or metastatic SCLC, had an Eastern Cooperative Oncology Group performance status of 1 and below, and had received two or more lines of previous therapy. Patients in KEYNOTE-028 were required to have a programmed death ligand 1 (PD-L1)-positive tumor. Patients received pembrolizumab (10 mg/kg every 2 weeks in KEYNOTE-028 or 200 mg every 3 weeks in KEYNOTE-158) for up to 2 years. The primary end point was objective response rate per Response Evaluation Criteria in Solid Tumors version 1.1, which is presented here per independent review. RESULTS: Eighty-three patients who had received two or more lines of previous therapy (KEYNOTE-028, n = 19; KEYNOTE-158, n = 64) were included. Median follow-up duration was 7.7 (range, 0.5-48.7) months. Objective response rate was 19.3% (95% confidence interval: 11.4-29.4); two patients had complete response (one with a PD-L1-positive tumor), and 14 patients had partial response (13 with PD-L1-positive tumors). The median duration of response was not reached (range, 4.1‒35.8+ mo; plus sign indicates ongoing response); 61% of responders had responses lasting 18 months or longer. Fifty-one patients (61.4%) experienced any-grade treatment-related adverse events; eight patients (9.6%) had grade 3 or higher events. CONCLUSIONS:Pembrolizumab exhibited durable antitumor activity in a subset of patients with recurrent or metastatic SCLC who had undergone two or more previous lines of therapy, regardless of PD-L1 expression. Pembrolizumab was well tolerated.
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