@article{5bd650ac115c49a985d8c99af35f2390,
title = "Five-year survival outcomes for patients with advanced melanoma treated with pembrolizumab in KEYNOTE-001",
abstract = "Background: Pembrolizumab demonstrated robust antitumor activity and safety in the phase Ib KEYNOTE-001 study (NCT01295827) of advanced melanoma. Five-year outcomes in all patients and treatment-naive patients are reported herein. Patients whose disease progressed following initial response and who received a second course of pembrolizumab were also analyzed. Patients and methods: Patients aged ≥18 years with previously treated or treatment-naive advanced/metastatic melanoma received pembrolizumab 2 mg/kg every 3 weeks, 10 mg/kg every 3 weeks, or 10 mg/kg every 2 weeks until disease progression, intolerable toxicity, or patient/investigator decision to withdraw. Kaplan-Meier estimates of overall survival (OS) and progression-free survival (PFS) were calculated. Objective response rate and PFS were based on immune-related response criteria by investigator assessment (data cut-off, September 1, 2017). Results: KEYNOTE-001 enrolled 655 patients with melanoma; median follow-up was 55 months. Estimated 5-year OS was 34% in all patients and 41% in treatment-naive patients; median OS was 23.8 months (95% CI, 20.2-30.4) and 38.6 months (95% CI, 27.2-not reached), respectively. Estimated 5-year PFS rates were 21% in all patients and 29% in treatment-naive patients; median PFS was 8.3 months (95% CI, 5.8-11.1) and 16.9 months (95% CI, 9.3-35.5), respectively. Median response duration was not reached; 73% of all responses and 82% of treatment-naive responses were ongoing at data cut-off; the longest response was ongoing at 66 months. Four patients [all with prior response of complete response (CR)] whose disease progressed during observation subsequently received second-course pembrolizumab. One patient each achieved CR and partial response (after data cut-off). Treatment-related AEs (TRAEs) occurred in 86% of patients and resulted in study discontinuation in 7.8%; 17% experienced grade 3/4 TRAE. Conclusions: This 5-year analysis of KEYNOTE-001 represents the longest follow-up for pembrolizumab to date and confirms the durable antitumor activity and tolerability of pembrolizumab in advanced melanoma. Clinical Trial Registry: ClinicalTrials.gov, NCT01295827.",
keywords = "long-term follow-up, melanoma, metastatic, overall survival, pembrolizumab, treatment-naive",
author = "O. Hamid and C. Robert and A. Daud and Hodi, {F. S.} and Hwu, {W. J.} and R. Kefford and Wolchok, {J. D.} and P. Hersey and R. Joseph and Weber, {J. S.} and R. Dronca and Mitchell, {T. C.} and A. Patnaik and Zarour, {H. M.} and Joshua, {A. M.} and Q. Zhao and E. Jensen and S. Ahsan and N. Ibrahim and A. Ribas",
note = "Funding Information: The authors thank Maxine Giannotti and Cathie Scalzo for study support, Scott Diede and Scot Ebbinghaus for study design and oversight, and Andrea L. Webber, Michael Nebozhyn (all from Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA), and Robin Mogg for assistance with biomarker analyses. Medical writing and/or editorial assistance was provided by Doyel Mitra, PhD, and Cathy Winter, PhD of the ApotheCom pembrolizumab team (Yardley, PA). This assistance was funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. This research was funded in part through the NIH/NCI Cancer Center Support Grant P30 CA0087 48. Funding for this research was provided by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. Funding Information: Funding for this study was provided by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. No grant number is applicable. Funding Information: Funding for this study was provided by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA; no grant number is applicable. The sponsor collaborated with academic advisers to design the study and gather, analyze, and interpret the results. All authors had full access to all study data and approved the decision to submit the manuscript for publication. Funding Information: OH reports personal fees from Merck, during the conduct of the study; personal fees from Amgen, Novartis, Genentech Roche, BMS, and Array Biopharma; and other support from Astra Zeneca, BMS, Celldex, Genentech Roche, lmmunocore, lncyte, Merck, Merck Sereno, Medlmmune, Novartis, Pfizer, and Rinat outside the submitted work. CR reports personal fees from BMS, Pierre Fabre, Novartis, Amgen, Merck, and Roche, outside the submitted work. AD reports grants and personal fees from Merck, BMS, personal fees from Amgen, and grants from Incyte, during the conduct of the study. FSH reports clinical trial support to the institution from BMS during the conduct of the study; grants to the institution and personal fees from BMS, and personal fees from Merck, EMD Serono, Novartis, Celldex, Amgen, Genentech/Roche, Incyte, Apricity, Bayer, Aduro, Partners Therapeutics, Sanofi, Pfizer, Pionyr, Seven Hills Pharma, Verastern, Compass Therapeutics, Takeda, and Surface, outside the submitted work. FSH has received personal fees from and holds equity in Torque. FSH holds a patent pending with royalties paid for Methods for Testing MICA Related Disorders (#20100111973), issued patents Tumor antigens and uses thereof (#7250291), and Therapeutic Peptides (#9402905); and patents pending for Angiopoiten-2 Biomarkers Predictive of Anti-immune checkpoint response (#20170248603), Compositions and Methods for Identification, Assessment, Prevention, and Treatment of Melanoma using PD-L1 Isoforms (#20160340407), Therapeutic Peptides (#20160046716, #20140004112, #20170022275, #20170008962), and Methods of Using Pembrolizumab and Trebananib (#Pending). RK reports other support from Merck during the conduct of the study and other support from BMS, Novartis, Amgen, and Teva outside the submitted work. JDW reports grants and personal fees from Merck during the conduct of the study; personal fees from and stock ownership in BeiGene, Apricity, and Adaptive Biotech; is the cofounder of, has stock ownership in, and has received personal fees from Potenza, Tizona, Imvaq, and Trieza; grants and personal fees from BMS, Genetech, MedImmune, and personal fees from Surface Oncology, Polaris, Polonoma, Array BioPharma, Ascentage, Chugai, FStar, Sellas Life Sciences, Serametrix, Neon, Eli Lilly, Kleo, Psioxus, Syndax, Recepta, Amgen, Puretech, Elucida, Ono, and Celgene outside the submitted work. JDW holds patents and receives royalties for Xenogeneic DNA vaccines, anti-CTLA4 antibodies, and anti-GITR antibodies and methods of use thereof. JDW has patents pending for Alphavirus, NewCastle Disease Viruses for Cancer Therapy, Genomic Signature to Identify Responders to Ipilimumab in Melanoma, Engineered Vaccinia Viruses for Cancer Immunotherapy, Anti-CD40 agonist mAb fused to Monophosphoryl Lipid A (MPL) for cancer therapy, and CAR+ T cells targeting differentiation antigens as means to treat cancer. RJ reports other support from Merck as a consultant outside the submitted work. JSW reports personal fees from Merck, BMS, Genentech, Celldex, Pfizer, and AstraZeneca outside the submitted work. In addition, JSW is named on a PD-1 biomarker patent issued by Biodesix. TCM reports personal fees from BMS, Aduro, Merck, and lncyte, outside the submitted work. AP reports grants from Merck during the conduct of the study. HZ reports grants from BMS, Merck, Tesaro, and Imcheck outside the submitted work. QZ, EJ, and SA are employees of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. NI is an employee and stockholder of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, and a stockholder of GlaxoSmithKline. AR reports financial support from Merck for the conduct of the clinical trial through an institutional contract with UCLA, during the conduct of the study and personal fees from Merck outside the submitted work. WJH, PH, RD, and AJ have nothing to disclose.",
year = "2019",
doi = "10.1093/annonc/mdz011",
language = "English (US)",
volume = "30",
pages = "582--588",
journal = "Annals of Oncology",
issn = "0923-7534",
publisher = "Oxford University Press",
number = "4",
}