Pembrolizumab as first-line therapy for patients with PD-L1-positive advanced non-small cell lung cancer: a phase 1 trial |
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| Institution: | 1. Medical Oncology, Westmead Hospital and the University of Sydney, Sydney, Australia;2. Hematology/Oncology, David Geffen School of Medicine at UCLA, Santa Monica, USA;3. Department of Medicine, Princess Margaret Cancer Centre, Toronto, Canada;4. Hematology/Oncology, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York;5. Oncology and Hematology Clinical Research, South Texas Accelerated Research Therapeutics, San Antonio;6. Hematology/Oncology, Dana-Farber Cancer Institute, Boston;7. Medical Oncology, Yale University, New Haven, USA;8. Hematology and Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea;9. Thoracic Oncology, Vanderbilt Ingram Cancer Center, Nashville, USA;10. Medical Oncology, Vall d’Hebron University Hospital, Vall d’Hebron Institute of Oncology (VHIO), Barcelona;11. Medical Oncology, Catalan Institute of Oncology Badalona, Badalona, Spain;12. Medical Oncology, Merck & Co., Inc., Kenilworth;13. Companion Diagnostics, Dako, an Agilent Technologies Company, Carpinteria;14. Thoracic Oncology, Columbia University, New York, USA |
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| Abstract: | BackgroundPembrolizumab improved survival as first- and second-line therapy compared with chemotherapy in patients with highly programmed death ligand 1 (PD-L1) expressing advanced non-small cell lung cancer (NSCLC). We report the long-term safety and clinical activity of pembrolizumab as first-line therapy for patients with advanced NSCLC and the correlation between PD-L1 expression and efficacy.Patients and methodsIn the open-label phase 1b KEYNOTE-001 trial, treatment-naive patients with advanced NSCLC whose tumors expressed PD-L1 (≥1% staining, assessed using a prototype assay) were randomly assigned to intravenous pembrolizumab 2 or 10 mg/kg every 3 (Q3W) or 2 (Q2W) weeks. Response was assessed per central RECIST v1.1 every 9 weeks in all patients who received ≥1 pembrolizumab dose. Using pre-treatment tumor tissue, a clinical assay quantified the percentage of tumor cells expressing PD-L1 as tumor proportion score (TPS).ResultsBetween 1 March 2013 and 18 September 2015, 101 patients received pembrolizumab 2 mg/kg Q3W (n = 6), 10 mg/kg Q3W (n = 49), or 10 mg/kg Q2W (n = 46). Of these, 27 (26.7%) had TPS ≥50%, 52 (51.5%) had TPS 1%–49%, and 12 (11.9%) had TPS <1%. The objective response rate (ORR) was 27% (27/101, 95% CI 18–37) and median overall survival was 22.1 months (95% CI 17.1–27.2). In patients with PD-L1 TPS ≥50%, ORR, 12-month PFS, and 12-month OS were higher 14/27 (51.9%; 95% CI 32%–71%), 54%, and 85%, respectively] than the overall population 27/101 (26.7%; 95% CI 18.4%–36.5%), 35%, 71%]. Pembrolizumab was well tolerated, with only 12 (11.9%) patients experiencing grade 3/4 treatment-related adverse events and no treatment-related deaths.ConclusionsPembrolizumab provides promising long-term OS benefit with a manageable safety profile for PD-L1-expressing treatment-naive advanced NSCLC, with greatest efficacy observed in patients with TPS ≥50%.Clinical trial name and numberKEYNOTE-001 (ClinicalTrials.gov, NCT01295827). |
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