PMID- 31446994 OWN - NLM STAT- MEDLINE DCOM- 20200713 LR - 20200713 IS - 1872-8332 (Electronic) IS - 0169-5002 (Linking) VI - 135 DP - 2019 Sep TI - Safety and efficacy of pembrolizumab monotherapy in elderly patients with PD-L1-positive advanced non-small-cell lung cancer: Pooled analysis from the KEYNOTE-010, KEYNOTE-024, and KEYNOTE-042 studies. PG - 188-195 LID - S0169-5002(19)30527-6 [pii] LID - 10.1016/j.lungcan.2019.07.004 [doi] AB - OBJECTIVES: Most lung cancer diagnoses occur in elderly patients, who are underrepresented in clinical trials. We present a pooled analysis of safety and efficacy in elderly patients (>/=75 years) who received pembrolizumab (a programmed death 1 inhibitor) for advanced non-small-cell lung cancer (NSCLC) with programmed death ligand 1 (PD-L1)‒positive tumors. METHODS: The pooled analysis included patients aged >/=18 years with advanced NSCLC with PD-L1-positive tumors from the KEYNOTE-010 (NCT01905657), KEYNOTE-024 (NCT02142738), and KEYNOTE-042 (NCT02220894) studies. In KEYNOTE-010, patients were randomized to pembrolizumab 2 or 10 mg/kg every 3 weeks (Q3W) or docetaxel, as second- or later-line therapy. In KEYNOTE-024 and KEYNOTE-042, patients were randomized to first-line pembrolizumab 200 mg Q3W or platinum-based chemotherapy. Overall survival (OS) was estimated by the Kaplan-Meier method, and safety data were summarized in elderly patients (>/=75 years). RESULTS: The analysis included 264 elderly patients with PD-L1-positive tumors (PD-L1 tumor proportion score [TPS] >/=1%); among these, 132 had PD-L1 TPS >/= 50%. Pembrolizumab improved OS among elderly patients with PD-L1 TPS >/= 1% (hazard ratio [HR], 0.76 [95% CI, 0.56-1.02]) and PD-L1 TPS >/= 50% (HR, 0.40 [95% CI, 0.25-0.64]). Pembrolizumab as first-line therapy also improved OS among elderly patients with PD-L1 TPS >/= 50% (from KEYNOTE-024 and KEYNOTE-042) compared with chemotherapy (HR, 0.41 [95% CI, 0.23‒0.73]). Pembrolizumab was associated with fewer treatment-related adverse events (AEs) in elderly patients (overall, 68.5% vs 94.3%; grade >/=3, 24.2% vs 61.0%) versus chemotherapy. Immune-mediated AEs and infusion reactions were more common with pembrolizumab versus chemotherapy (overall, 24.8% vs 6.7%; grade 3‒4: 9.4% vs 0%; no grade 5 events). CONCLUSIONS: In this pooled analysis of elderly patients with advanced NSCLC with PD-L1‒positive tumors, pembrolizumab improved OS versus chemotherapy, with a more favorable safety profile. Outcomes with pembrolizumab in patients >/=75 years were comparable to those in the overall populations in the individual studies. CI - Copyright (c) 2019 Elsevier B.V. All rights reserved. FAU - Nosaki, Kaname AU - Nosaki K AD - National Hospital Organization Kyushu Cancer Center, Minami-ku, Fukuoka-shi, Fukuoka 811-1395, Japan. Electronic address: knosaki@east.ncc.go.jp. FAU - Saka, Hideo AU - Saka H AD - National Hospital Organization Nagoya Medical Center, 4-1-1 Sannomaru, Naka-ku, Nagoya, Aichi 460-0001, Japan. Electronic address: hideosaka@me.com. FAU - Hosomi, Yukio AU - Hosomi Y AD - Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, 3-18-22 Honkomagome, Bunkyo-ku, Tokyo 113-8677, Japan. Electronic address: yhosomi@cick.jp. FAU - Baas, Paul AU - Baas P AD - The Netherlands Cancer Institute, Postbus 90203, 1006 BE Amsterdam, the Netherlands. Electronic address: p.baas@nki.nl. FAU - de Castro, Gilberto Jr AU - de Castro G Jr AD - Instituto do Cancer do Estado de Sao Paulo, Av. Dr. Arnaldo, 251 - Cerqueira Cesar, Sao Paulo, SP 01246-000, Brazil. Electronic address: gilberto.castro@usp.br. FAU - Reck, Martin AU - Reck M AD - Lung Clinic Grosshansdorf, Airway Research Center North (ARCN), member of the German Center for Lung Research (DZL), Wohrendamm 80, 22927 Grosshansdorf, Germany. Electronic address: M.Reck@lungenclinic.de. FAU - Wu, Yi-Long AU - Wu YL AD - Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital, and Guangdong Academy of Medical Sciences, Guangdong, 106 Zhongshan 2nd Rd, Yuexiu Qu, Guangzhou Shi, Guangdong Sheng 510080, China. Electronic address: syylwu@live.cn. FAU - Brahmer, Julie R AU - Brahmer JR AD - Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, 1650 Orleans St, Baltimore, 21287 MD, USA. Electronic address: brahmju@jhmi.edu. FAU - Felip, Enriqueta AU - Felip E AD - Vall d'Hebron University Hospital, P. Vall d'Hebron, 119-129, 08035 and IOB Quiron, Barcelona, Spain. Electronic address: efelip@vhio.net. FAU - Sawada, Takeshi AU - Sawada T AD - MSD K.K., Kitanomaru Square, 1-13-12, Kudan Kita, Chiyoda-ku, Tokyo 102-8667, Japan. Electronic address: takeshi.sawada@merck.com. FAU - Noguchi, Kazuo AU - Noguchi K AD - MSD K.K., Kitanomaru Square, 1-13-12, Kudan Kita, Chiyoda-ku, Tokyo 102-8667, Japan. Electronic address: kazuo.noguchi@merck.com. FAU - Han, Shi Rong AU - Han SR AD - MSD K.K., Kitanomaru Square, 1-13-12, Kudan Kita, Chiyoda-ku, Tokyo 102-8667, Japan. Electronic address: shi.rong.han@merck.com. FAU - Piperdi, Bilal AU - Piperdi B AD - Merck & Co., Inc., 2000 Galloping Hill Rd, Kenilworth, NJ 07033, USA. Electronic address: bilal.piperdi@merck.com. FAU - Kush, Debra A AU - Kush DA AD - Merck & Co., Inc., 2000 Galloping Hill Rd, Kenilworth, NJ 07033, USA. Electronic address: debra_kush@merck.com. FAU - Lopes, Gilberto AU - Lopes G AD - Sylvester Comprehensive Cancer Center at the University of Miami, 1475 NW 12th Ave, Miami, FL 33136, USA. Electronic address: glopes.md@gmail.com. LA - eng PT - Journal Article PT - Meta-Analysis PT - Research Support, Non-U.S. Gov't DEP - 20190708 PL - Ireland TA - Lung Cancer JT - Lung cancer (Amsterdam, Netherlands) JID - 8800805 RN - 0 (Antibodies, Monoclonal, Humanized) RN - 0 (Antineoplastic Agents, Immunological) RN - 0 (B7-H1 Antigen) RN - 0 (Biomarkers, Tumor) RN - 0 (CD274 protein, human) RN - DPT0O3T46P (pembrolizumab) SB - IM CIN - Ann Transl Med. 2019 Dec;7(Suppl 8):S282. PMID: 32016001 CIN - Ann Transl Med. 2019 Dec;7(Suppl 8):S383. PMID: 32016101 CIN - Ann Transl Med. 2020 Jun;8(12):778. PMID: 32647703 MH - Aged MH - Aged, 80 and over MH - Antibodies, Monoclonal, Humanized/administration & dosage/adverse effects/*therapeutic use MH - Antineoplastic Agents, Immunological/administration & dosage/adverse effects/*therapeutic use MH - B7-H1 Antigen/genetics/*metabolism MH - Biomarkers, Tumor MH - Carcinoma, Non-Small-Cell Lung/diagnosis/*drug therapy/*metabolism/mortality MH - Female MH - Humans MH - Lung Neoplasms/diagnosis/*drug therapy/*metabolism/mortality MH - Male MH - Mutation MH - Neoplasm Staging MH - Randomized Controlled Trials as Topic MH - Treatment Outcome OTO - NOTNLM OT - Chemotherapy OT - Elderly OT - Non-small-cell lung cancer OT - Pembrolizumab OT - Phase 3 OT - Pooled analysis EDAT- 2019/08/27 06:00 MHDA- 2020/07/14 06:00 CRDT- 2019/08/27 06:00 PHST- 2019/05/06 00:00 [received] PHST- 2019/07/03 00:00 [revised] PHST- 2019/07/06 00:00 [accepted] PHST- 2019/08/27 06:00 [entrez] PHST- 2019/08/27 06:00 [pubmed] PHST- 2020/07/14 06:00 [medline] AID - S0169-5002(19)30527-6 [pii] AID - 10.1016/j.lungcan.2019.07.004 [doi] PST - ppublish SO - Lung Cancer. 2019 Sep;135:188-195. doi: 10.1016/j.lungcan.2019.07.004. Epub 2019 Jul 8.