Hypersensitivity Reactions to Selpercatinib Treatment With or Without Prior Immune Checkpoint Inhibitor Therapy in Patients With NSCLC in LIBRETTO-001.

Autor:	McCoach CE; Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, California; Present Address: Genentech, Inc., South San Francisco, California. Electronic address: caroline.mccoach@ucsf.edu., Rolfo C; Greenebaum Comprehensive Cancer Center, Experimental Therapeutics Program, School of Medicine, University of Maryland, Baltimore, Maryland; Present Address: Center for Thoracic Oncology at Tisch Cancer Institute, Mount Sinai Health System and Icahn School of Medicine at Mount Sinai, New York, New York., Drilon A; Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, New York., Lacouture M; Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, New York., Besse B; Department of Cancer Medicine, Gustave Roussy Cancer Campus, Villejuif, France., Goto K; Department of Thoracic Oncology, National Cancer Center Hospital East, Kashiwa, Japan., Zhu VW; Department of Medicine, Division of Hematology and Oncology, University of California Irvine, Orange, California., Tan DSW; National Cancer Centre Singapore, Duke-National University of Singapore Medical School, Singapore., Farajian S; Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, California., Potter LA; Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, California; Present Address: Davis School of Medicine, University of California, Sacramento, Sacramento, California., Kherani JF; Loxo Oncology, Inc., a wholly owned subsidiary of Eli Lilly and Company, Stamford, Connecticut., Soldatenkova V; Eli Lilly and Company, Indianapolis, Indiana., Olek EA; Loxo Oncology, Inc., a wholly owned subsidiary of Eli Lilly and Company, Stamford, Connecticut., Muehlenbein CE; Eli Lilly and Company, Indianapolis, Indiana., Park K; Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
Jazyk:	angličtina
Zdroj:	Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer [J Thorac Oncol] 2022 Jun; Vol. 17 (6), pp. 768-778. Date of Electronic Publication: 2022 Feb 17.
DOI:	10.1016/j.jtho.2022.02.004
Abstrakt:	Introduction: Immune checkpoint inhibitor (ICI) therapy has been found to increase the risk/severity of immune-mediated adverse events with subsequent kinase inhibitor treatment in oncogenically driven cancers. We explored the risk for hypersensitivity with selpercatinib, a first-in-class highly selective and potent, central nervous system-active RET inhibitor, in prior ICI-treated patients with RET fusion-positive NSCLC compared with their ICI-naive counterparts. Methods: Data from patients enrolled by December 16, 2019, in the ongoing phase 1/2 LIBRETTO-001 (NCT03157128) trial were analyzed for hypersensitivity reactions reported using preferred terms of hypersensitivity/drug hypersensitivity and defined as a constellation of symptoms/findings characterized by maculopapular rash, often preceded by fever with arthralgias/myalgias, followed by greater than or equal to 1 of the following signs/symptoms: thrombocytopenia, increased aspartate aminotransferase or alanine aminotransferase, hypotension, tachycardia, or increased creatinine. Results: Of 329 patients, 22 (7%) who experienced a grade 1 to 3 hypersensitivity reaction that met the defined constellation of events were attributed to selpercatinib by investigators, and more often in prior ICI-treated (n = 17, 77%) than ICI-naive (n = 5, 23%) patients. There were 19 patients with selpercatinib-related hypersensitivity who resumed selpercatinib post-hypersensitivity with dose modification/supportive care. Furthermore, 17 patients, of whom 14 received prior ICI therapy, were still on treatment at twice daily doses of 40 mg (n = 5), 80 mg (n = 4), 120 mg (n = 4), and 160 mg (n = 4). Conclusions: Rates of selpercatinib-related hypersensitivity were low overall and, as with other kinase inhibitors, occurred predominantly in prior ICI-treated patients. Hypersensitivity to selpercatinib can be managed with supportive care measures regardless of prior ICI status and is reversible. (Copyright © 2022 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu