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      A Case of Nonsmall-Cell Lung Cancer with Anaphylaxis after 41 Courses of Pembrolizumab along with Adrenal Insufficiency as an Immune-Related Adverse Event

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          Abstract

          In this report, we present a case of nonsmall-cell lung cancer with anaphylaxis after 41 courses of pembrolizumab along with adrenal insufficiency as an immune-related adverse event (irAE). A 73-year-old man with no allergic disease started pembrolizumab for postoperative recurrence of lung cancer. After four courses, tumor shrinkage was observed and maintained thereafter. After the 39th course, his serum sodium level and random serum cortisol level decreased. Adrenal insufficiency was considered; however, the patient was asymptomatic. Furthermore, his serum sodium level improved spontaneously; therefore, he was followed up. At the end of the 40th course, rhinorrhea and pharyngeal discomfort were noted; however, they were mild and resolved spontaneously. Immediately after administration of the 41st course, he developed pembrolizumab-induced anaphylaxis with percutaneous oxygen saturation decreased. The symptoms quickly improved after intramuscular adrenaline were administered and did not recur. Three months after discharge, the patient was urgently examined for vomiting and anorexia. His serum sodium levels decreased to 119 mEq/L, and an adrenocorticotropic hormone stimulation test was performed. It showed a low response, and the patient was diagnosed with secondary adrenal insufficiency as an irAE of pembrolizumab and treated with hydrocortisone, which quickly improved his serum sodium levels and symptoms. When adrenal insufficiency develops due to irAEs, patients may be susceptible to allergic reactions.

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          Most cited references19

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          Pembrolizumab versus chemotherapy for previously untreated, PD-L1-expressing, locally advanced or metastatic non-small-cell lung cancer (KEYNOTE-042): a randomised, open-label, controlled, phase 3 trial

          First-line pembrolizumab monotherapy improves overall and progression-free survival in patients with untreated metastatic non-small-cell lung cancer with a programmed death ligand 1 (PD-L1) tumour proportion score (TPS) of 50% or greater. We investigated overall survival after treatment with pembrolizumab monotherapy in patients with a PD-L1 TPS of 1% or greater.
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            The role of PD-L1 expression as a predictive biomarker: an analysis of all US Food and Drug Administration (FDA) approvals of immune checkpoint inhibitors

            The development of immune checkpoint inhibitors has changed the treatment paradigm for advanced cancers across many tumor types. Despite encouraging and sometimes durable responses in a subset of patients, most patients do not respond. Tumors have adopted the PD-1/PD-L1 axis for immune escape to facilitate tumor growth, which can be leveraged as a potential target for immune checkpoint inhibitors. On this basis, PD-L1 protein expression on tumor or immune cells emerged as the first potential predictive biomarker for sensitivity to immune checkpoint blockade. The goal of our study was to evaluate PD-L1 as a predictive biomarker based on all US Food and Drug Administration (FDA) drug approvals of immune checkpoint inhibitors. We evaluated the primary studies associated with 45 FDA drug approvals from 2011 until April 2019. In total, there were approvals across 15 tumor types. Across all approvals, PD-L1 was predictive in only 28.9% of cases, and was either not predictive (53.3%) or not tested (17.8%) in the remaining cases. There were 9 FDA approvals linked to a specific PD-L1 threshold and companion diagnostic: bladder cancer (N = 3), non-small cell lung cancer (N = 3), triple-negative breast cancer (N = 1), cervical cancer (N = 1), and gastric/gastroesophageal junction cancer (N = 1) with 8 of 9 (88.9%) with immune checkpoint inhibitor monotherapy. The PD-L1 thresholds were variable both within and across tumor types using several different assays, including approvals at the following PD-L1 thresholds: 1, 5, and 50%. PD-L1 expression was also measured in a variable fashion either on tumor cells, tumor-infiltrating immune cells, or both. In conclusion, our findings indicate that PD-L1 expression as a predictive biomarker has limitations and that the decision to pursue testing must be carefully implemented for clinical decision-making.
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              Endocrine toxicities of immune checkpoint inhibitors

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                Author and article information

                Journal
                Case Rep Oncol
                Case Rep Oncol
                CRO
                Case Reports in Oncology
                S. Karger AG (Allschwilerstrasse 10, P.O. Box · Postfach · Case postale, CH–4009, Basel, Switzerland · Schweiz · Suisse, Phone: +41 61 306 11 11, Fax: +41 61 306 12 34, karger@karger.com )
                1662-6575
                Sep-Dec 2022
                19 September 2022
                19 September 2022
                : 15
                : 3
                : 804-808
                Affiliations
                Department of Pulmonary Medicine, Thoracic Center, St. Luke's International Hospital, Tokyo, Japan
                Author notes
                *Tomoaki Nakamura, tonaka@ 123456luke.ac.jp
                Article
                cro-0015-0804
                10.1159/000526561
                9941790
                36825102
                a9ce3df1-e476-4e05-995e-b5d24d45f3b1
                Copyright © 2022 by The Author(s). Published by S. Karger AG, Basel

                This article is licensed under the Creative Commons Attribution-NonCommercial-4.0 International License (CC BY-NC) (http://www.karger.com/Services/OpenAccessLicense). Usage and distribution for commercial purposes requires written permission.

                History
                : 17 July 2022
                : 4 August 2022
                : 2022
                Page count
                Figures: 1, References: 12, Pages: 5
                Funding
                No funding sources were used in the conception, composition, editing, or submission of this manuscript.
                Categories
                Case Report

                Oncology & Radiotherapy
                lung cancer,pembrolizumab,anaphylaxis,adrenal insufficiency,immune-related adverse event

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