Hypersensitivity reactions to selpercatinib treatment with or without prior immune checkpoint inhibitor therapy in patients with NSCLC in LIBRETTO-001 Journal Article
| Authors: | McCoach, C. E.; Rolfo, C.; Drilon, A.; Lacouture, M.; Besse, B.; Goto, K.; Zhu, V. W.; Tan, D. S. W.; Farajian, S.; Potter, L. A.; Kherani, J. F.; Soldatenkova, V.; Olek, E. A.; Muehlenbein, C. E.; Park, K. |
| Article Title: | Hypersensitivity reactions to selpercatinib treatment with or without prior immune checkpoint inhibitor therapy in patients with NSCLC in LIBRETTO-001 |
| Abstract: | 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. |
| Keywords: | pyridines; protein kinase inhibitor; carcinoma, non-small-cell lung; lung neoplasms; protein kinase inhibitors; lung tumor; pyrazole derivative; pyrazoles; protein ret; proto-oncogene proteins c-ret; pyridine derivative; supportive care; non small cell lung cancer; hypersensitivity; immune checkpoint inhibitor; humans; human; immune checkpoint inhibitors; non–small-cell lung cancer; selpercatinib |
| Journal Title: | Journal of Thoracic Oncology |
| Volume: | 17 |
| Issue: | 6 |
| ISSN: | 1556-0864 |
| Publisher: | Elsevier Inc. |
| Date Published: | 2022-06-01 |
| Start Page: | 768 |
| End Page: | 778 |
| Language: | English |
| DOI: | 10.1016/j.jtho.2022.02.004 |
| PUBMED: | 35183775 |
| PROVIDER: | scopus |
| PMCID: | PMC11083849 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 July 2022 -- Source: Scopus |
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