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      KEYNOTE‐025: Phase 1b study of pembrolizumab in Japanese patients with previously treated programmed death ligand 1–positive advanced non–small‐cell lung cancer

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          Abstract

          Pembrolizumab, a humanized monoclonal antibody against programmed death 1 ( PD‐1), has been shown to improve overall survival ( OS) in patients with previously treated advanced non–small‐cell lung cancer ( NSCLC) with programmed death ligand 1 ( PD‐L1) tumor proportion score ( TPS) ≥1%. We report safety and efficacy results from the phase 1b KEYNOTE‐025 study, which evaluated pembrolizumab in Japanese patients with previously treated NSCLC. Eligible patients had histologically/cytologically confirmed advanced NSCLC with PD‐L1 TPS ≥1% and had received ≥1 platinum‐doublet chemotherapy. Patients received pembrolizumab 10 mg/kg once every 3 weeks for 2 years or until disease progression/unacceptable toxicity. Primary objectives were to evaluate the safety of pembrolizumab in patients with PD‐L1 TPS ≥1% and the objective response rate ( ORR) per RECIST version 1.1 in patients with PD‐L1 TPS ≥50%. Thirty‐eight patients were enrolled and received ≥1 pembrolizumab dose. The median (range) age was 66.0 (41‐78) years, and 61% had received ≥2 prior systemic therapies. Eleven patients (29%) experienced grade 3‐5 treatment‐related adverse events (AE); 9 patients (24%) experienced immune‐mediated AE and infusion reactions, with pneumonitis (11%; any grade) being most common. Among evaluable patients with PD‐L1 TPS ≥50% (n = 11), ORR was 27% (95% CI, 6‐61). Among evaluable patients with PD‐L1 TPS ≥1% (n = 37), ORR was 22% (95% CI, 10‐38). Median (95% CI) progression‐free survival and OS were 3.9 (2.0‐6.2) months and 19.2 (8.0‐26.7) months, respectively. In summary, pembrolizumab was generally well tolerated and showed promising antitumor activity in Japanese patients with previously treated PD‐L1–expressing NSCLC. Outcomes were consistent with those from the phase 3 KEYNOTE‐010 study. (Trial registration number: ClinicalTrials.gov, NCT02007070.)

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          Checkpoint Inhibitors in Metastatic EGFR-Mutated Non-Small Cell Lung Cancer-A Meta-Analysis.

          We performed a meta-analysis to assess the role of immune checkpoint inhibitors as second-line therapy in EGFR-mutant advanced NSCLC.
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            Incidence of Programmed Cell Death 1 Inhibitor-Related Pneumonitis in Patients With Advanced Cancer: A Systematic Review and Meta-analysis.

            Programmed cell death 1 (PD-1) inhibitor-related pneumonitis is a rare but clinically serious and potentially life-threatening adverse event. Little is known about its incidence across different tumor types and treatment regimens.
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              Immune-checkpoint inhibitors associated with interstitial lung disease in cancer patients

              Immunotherapy is becoming a standard of care for many cancers. Immune-checkpoint inhibitors (ICI) can generate immune-related adverse events. Interstitial lung disease (ILD) has been identified as a rare but potentially severe event. Between December 2015 and April 2016, we conducted a retrospective study in centres experienced in ICI use. We report the main features of ICI–ILD with a focus on clinical presentation, radiological patterns and therapeutic strategies. We identified 64 (3.5%) out of 1826 cancer patients with ICI–ILD. Patients mainly received programmed cell death-1 inhibitors. ILD usually occurred in males, and former or current smokers, with a median age of 59 years. We observed 65.6% grade 2/3 severity, 9.4% grade 4 severity and 9.4% fatal ILD. The median (range) time from initiation of immunotherapy to ILD was 2.3 (0.2−27.4) months. Onset tended to occur earlier in lung cancer versus melanoma: median 2.1 and 5.2 months, respectively (p=0.02). Ground-glass opacities (81.3%) were the predominant lesions, followed by consolidations (53.1%). Organising pneumonia (23.4%) and hypersensitivity pneumonitis (15.6%) were the most common patterns. Overall survival at 6 months was 58.1% (95% CI 37.7–73.8%). ICI–ILD often occurs early and displays suggestive radiological features. As there is no clearly identified risk factor, oncologists need to diagnose and adequately treat this adverse event.
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                Author and article information

                Contributors
                mnishio@jfcr.or.jp
                Journal
                Cancer Sci
                Cancer Sci
                10.1111/(ISSN)1349-7006
                CAS
                Cancer Science
                John Wiley and Sons Inc. (Hoboken )
                1347-9032
                1349-7006
                16 February 2019
                March 2019
                : 110
                : 3 ( doiID: 10.1111/cas.2019.110.issue-3 )
                : 1012-1020
                Affiliations
                [ 1 ] Department of Thoracic Medical Oncology The Cancer Institute Hospital of Japanese Foundation for Cancer Research Tokyo Japan
                [ 2 ] Division of Thoracic Oncology Shizuoka Cancer Center Suntogun Japan
                [ 3 ] Department of Respiratory Medicine Kurashiki Central Hospital Kurashiki Japan
                [ 4 ] Department of Medical Oncology Faculty of Medicine Kindai University Osaka‐Sayama Japan
                [ 5 ] Department of Respiratory Medicine Miyagi Cancer Center Natori Japan
                [ 6 ] Department of Internal Medicine Division of Respirology, Neurology, and Rheumatology Kurume University Kurume Japan
                [ 7 ] Respiratory Medicine Kyushu Medical Center Fukuoka Japan
                [ 8 ] Department of Internal Medicine (Pulmonology) Niigata Cancer Center Hospital Niigata Japan
                [ 9 ] Department of Thoracic Oncology National Kyushu Cancer Center Fukuoka Japan
                [ 10 ] Thoracic Oncology Saitama Cancer Center Saitama Japan
                [ 11 ] Respiratory Medicine Kanazawa University Hospital Kanazawa Japan
                [ 12 ] Department of Thoracic Oncology Hyogo Cancer Center Akashi Japan
                [ 13 ] Oncology Science Unit MSD K.K. Tokyo Japan
                [ 14 ] Department of Respiratory Medicine Kanagawa Cardiovascular and Respiratory Center Yokohama Japan
                Author notes
                [*] [* ] Correspondence

                Makoto Nishio, Department of Thoracic Medical Oncology, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan.

                Email: mnishio@ 123456jfcr.or.jp

                Author information
                https://orcid.org/0000-0003-4969-4165
                https://orcid.org/0000-0002-2960-4364
                Article
                CAS13932
                10.1111/cas.13932
                6398876
                30618179
                e5f0120f-b98a-4abd-b933-7ea490c6571c
                © 2019 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

                History
                : 05 September 2018
                : 19 December 2018
                : 24 December 2018
                Page count
                Figures: 4, Tables: 3, Pages: 9, Words: 5986
                Categories
                Original Article
                Original Articles
                Clinical Research
                Custom metadata
                2.0
                cas13932
                March 2019
                Converter:WILEY_ML3GV2_TO_NLMPMC version:5.6.1 mode:remove_FC converted:04.03.2019

                Oncology & Radiotherapy
                immunotherapy,non–small‐cell lung cancer,pd‐l1,pembrolizumab,phase 1
                Oncology & Radiotherapy
                immunotherapy, non–small‐cell lung cancer, pd‐l1, pembrolizumab, phase 1

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