PMID- 29955135 OWN - NLM STAT- MEDLINE DCOM- 20190815 LR - 20220408 IS - 1532-1827 (Electronic) IS - 0007-0920 (Print) IS - 0007-0920 (Linking) VI - 119 IP - 2 DP - 2018 Jul TI - Efficacy and safety of pembrolizumab in recurrent/metastatic head and neck squamous cell carcinoma: pooled analyses after long-term follow-up in KEYNOTE-012. PG - 153-159 LID - 10.1038/s41416-018-0131-9 [doi] AB - BACKGROUND: Second-line treatment options for advanced head and neck squamous cell carcinoma (HNSCC) are limited. The phase Ib KEYNOTE-012 study evaluated the safety and the efficacy of pembrolizumab for the treatment of HNSCC after long-term follow-up. METHODS: Multi-centre, non-randomised trial included two HNSCC cohorts (initial and expansion) in which 192 patients were eligible. Patients received pembrolizumab 10 mg/kg every 2 weeks (initial cohort; N = 60) or 200 mg every 3 weeks (expansion cohort; N = 132). Co-primary endpoints were safety and overall response rate (ORR; RECIST v1.1; central imaging vendor review). RESULTS: Median follow-up was 9 months (range, 0.2-32). Treatment-related adverse events (AEs) of any grade and grade 3/4 occurred in 123 (64%) and 24 (13%) patients, respectively. No deaths were attributed to treatment-related AEs. ORR was 18% (34/192; 95% CI, 13-24%). Median response duration was not reached (range, 2+ to 30+ months); 85% of responses lasted >/=6 months. Overall survival at 12 months was 38%. CONCLUSIONS: Some patients received 2 years of treatment and the responses were ongoing for more than 30 months; the durable anti-tumour activity and tolerable safety profile, observed with long-term follow-up, support the use of pembrolizumab as a treatment for recurrent/metastatic HNSCC. FAU - Mehra, Ranee AU - Mehra R AD - Fox Chase Cancer Center, Philadelphia, PA, USA. rmehra1@jhmi.edu. AD - Johns Hopkins University, Baltimore, MD, USA. rmehra1@jhmi.edu. FAU - Seiwert, Tanguy Y AU - Seiwert TY AD - University of Chicago, Chicago, IL, USA. FAU - Gupta, Shilpa AU - Gupta S AD - H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA. AD - Masonic Cancer Centre, University of Minnesota, Minneapolis, MN, USA. FAU - Weiss, Jared AU - Weiss J AD - Lineberger Comprehensive Cancer Center at the University of North Carolina, Chapel Hill, NC, USA. FAU - Gluck, Iris AU - Gluck I AD - Sheba Medical Center, Ramat Gan, Israel. FAU - Eder, Joseph P AU - Eder JP AD - Yale Cancer Center, New Haven, CT, USA. FAU - Burtness, Barbara AU - Burtness B AD - Fox Chase Cancer Center, Philadelphia, PA, USA. AD - Yale Cancer Center, New Haven, CT, USA. FAU - Tahara, Makoto AU - Tahara M AD - National Cancer Center Hospital East, Chiba, Japan. FAU - Keam, Bhumsuk AU - Keam B AD - Seoul National University Hospital, Seoul, Republic of Korea. FAU - Kang, Hyunseok AU - Kang H AD - Johns Hopkins University, Baltimore, MD, USA. FAU - Muro, Kei AU - Muro K AD - Aichi Cancer Center Hospital, Nagoya, Japan. FAU - Geva, Ravit AU - Geva R AD - Sourasky Medical Center, Tel Aviv, Israel. FAU - Chung, Hyun Cheol AU - Chung HC AD - Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea. FAU - Lin, Chia-Chi AU - Lin CC AD - National Taiwan University Hospital, Taipei, Taiwan. FAU - Aurora-Garg, Deepti AU - Aurora-Garg D AD - Merck & Co., Inc, Kenilworth, NJ, USA. FAU - Ray, Archana AU - Ray A AD - Merck & Co., Inc, Kenilworth, NJ, USA. FAU - Pathiraja, Kumudu AU - Pathiraja K AD - Merck & Co., Inc, Kenilworth, NJ, USA. FAU - Cheng, Jonathan AU - Cheng J AD - Merck & Co., Inc, Kenilworth, NJ, USA. FAU - Chow, Laura Q M AU - Chow LQM AD - University of Washington, Seattle, WA, USA. FAU - Haddad, Robert AU - Haddad R AD - Dana-Farber Cancer Institute, Boston, MA, USA. LA - eng PT - Clinical Trial, Phase I PT - Journal Article PT - Multicenter Study DEP - 20180629 PL - England TA - Br J Cancer JT - British journal of cancer JID - 0370635 RN - 0 (Antibodies, Monoclonal, Humanized) RN - 0 (B7-H1 Antigen) RN - 0 (CD274 protein, human) RN - DPT0O3T46P (pembrolizumab) CIN - Ann Transl Med. 2019 Jul;7(Suppl 3):S75. PMID: 31576284 MH - Adult MH - Aged MH - Aged, 80 and over MH - Antibodies, Monoclonal, Humanized/*administration & dosage/adverse effects MH - B7-H1 Antigen/genetics MH - Drug-Related Side Effects and Adverse Reactions/classification/*pathology MH - Female MH - Follow-Up Studies MH - Gene Expression Regulation, Neoplastic/drug effects MH - Humans MH - Kaplan-Meier Estimate MH - Male MH - Middle Aged MH - Neoplasm Metastasis MH - Neoplasm Recurrence, Local/*drug therapy/genetics/pathology MH - Progression-Free Survival MH - Squamous Cell Carcinoma of Head and Neck/*drug therapy/genetics/pathology PMC - PMC6048158 COIS- T.Y.S., J.W., B.B., and H.K. have received research funding from Merck & Co., Inc. M.T. has received personal fees from Merck Sharp & Dohme. D.A.-G., A.R., K.P., and J.C. are employees Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. L.Q.C. has served as an advisor for and has received research from Merck & Co., Inc. R.H. has received research funding from Merck & Co., Inc., Bristol-Myers Squibb, Pfizer, and Astra Zeneca, and has served as a consultant for Merck & Co., Inc., Bristol-Myers Squibb, Pfizer, Celgene, Astra Zeneca, and Eisai. The remaining authors declare no competing interests. EDAT- 2018/06/30 06:00 MHDA- 2019/08/16 06:00 PMCR- 2019/07/17 CRDT- 2018/06/30 06:00 PHST- 2017/11/30 00:00 [received] PHST- 2018/05/10 00:00 [accepted] PHST- 2018/04/26 00:00 [revised] PHST- 2018/06/30 06:00 [pubmed] PHST- 2019/08/16 06:00 [medline] PHST- 2018/06/30 06:00 [entrez] PHST- 2019/07/17 00:00 [pmc-release] AID - 10.1038/s41416-018-0131-9 [pii] AID - 131 [pii] AID - 10.1038/s41416-018-0131-9 [doi] PST - ppublish SO - Br J Cancer. 2018 Jul;119(2):153-159. doi: 10.1038/s41416-018-0131-9. Epub 2018 Jun 29.