Hypersensitivity Reactions to Selpercatinib Treatment With or Without Prior Immune Checkpoint Inhibitor Therapy in Patients With NSCLC in LIBRETTO-001 |
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| Institution: | 1. Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, California;2. Present Address: Genentech, Inc., South San Francisco, California;3. Greenebaum Comprehensive Cancer Center, Experimental Therapeutics Program, School of Medicine, University of Maryland, Baltimore, Maryland;4. 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;5. Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, New York;6. Department of Cancer Medicine, Gustave Roussy Cancer Campus, Villejuif, France;7. Department of Thoracic Oncology, National Cancer Center Hospital East, Kashiwa, Japan;8. Department of Medicine, Division of Hematology and Oncology, University of California Irvine, Orange, California;9. National Cancer Centre Singapore, Duke-National University of Singapore Medical School, Singapore;10. Present Address: Davis School of Medicine, University of California, Sacramento, Sacramento, California;11. Loxo Oncology, Inc., a wholly owned subsidiary of Eli Lilly and Company, Stamford, Connecticut;12. Eli Lilly and Company, Indianapolis, Indiana;13. Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea |
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| Abstract: | IntroductionImmune 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.MethodsData 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.ResultsOf 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).ConclusionsRates 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. |
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| Keywords: | Hypersensitivity Selpercatinib Immune checkpoint inhibitor Non–small-cell lung cancer Supportive care |
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