Hypersensitivity Reactions to Selpercatinib Treatment with or Without Prior Immune Checkpoint Inhibitor Therapy in Patients with Non-Small-Cell Lung Cancer in LIBRETTO-001.
Name:
Publisher version
View Source
Access full-text PDFOpen Access
View Source
Check access options
Check access options
Author
McCoach, Caroline ERolfo, Christian
Drilon, Alexander
Lacouture, Mario
Besse, Benjamin
Goto, Koichi
Zhu, Viola W
Tan, Daniel Sw
Farajian, Stephanie
Potter, Laura A
Kherani, Jennifer F
Soldatenkova, Victoria
Olek, Elizabeth A
Muehlenbein, Catherine E
Park, Keunchil
Date
2022-02-17Journal
Journal of Thoracic OncologyPublisher
ElsevierType
Article
Metadata
Show full item recordAbstract
Introduction: Immune checkpoint inhibitor (ICI) therapy has been shown 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, CNS-active RET inhibitor, in prior ICI-treated patients with RET fusion-positive non-small-cell lung cancer (NSCLC) compared with their ICI-naïve counterparts. Methods: Data from patients enrolled by 16-December-2019 in the ongoing phase 1/2 LIBRETTO-001 (NCT03157128) trial were analyzed for hypersensitivity reactions reported using preferred terms hypersensitivity/drug hypersensitivity and defined as a constellation of symptoms/findings characterized by maculopapular rash, often preceded by fever with arthralgias/myalgias, followed by ≥1 of the following signs/symptoms: thrombocytopenia, increased AST/ALT, hypotension, tachycardia, and/or increased creatinine. Results: Twenty-two of 329 (7%) patients experienced a grade 1-3 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-naïve (n=5, 23%) patients. Nineteen patients with selpercatinib-related hypersensitivity resumed selpercatinib post-hypersensitivity with dose modification/supportive care. Seventeen 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 are reversible.Rights/Terms
Copyright © 2022. Published by Elsevier Inc.Keyword
Hypersensitivityimmune checkpoint inhibitor
non-small-cell lung cancer
selpercatinib
supportive care
Identifier to cite or link to this item
http://hdl.handle.net/10713/18105ae974a485f413a2113503eed53cd6c53
10.1016/j.jtho.2022.02.004
Scopus Count
Collections
Related articles
- Efficacy of immune checkpoint inhibitor therapy in patients with <i>RET</i> fusion-positive non-small-cell lung cancer.
- Authors: Bhandari NR, Hess LM, Han Y, Zhu YE, Sireci AN
- Issue date: 2021 Aug
- Patient-Reported Outcomes with Selpercatinib Among Patients with RET Fusion-Positive Non-Small Cell Lung Cancer in the Phase I/II LIBRETTO-001 Trial.
- Authors: Minchom A, Tan AC, Massarelli E, Subbiah V, Boni V, Robinson B, Wirth LJ, Hess LM, Jen MH, Kherani J, Olek E, McCoach CE
- Issue date: 2022 Feb 3
- Overcoming MET-Dependent Resistance to Selective RET Inhibition in Patients with RET Fusion-Positive Lung Cancer by Combining Selpercatinib with Crizotinib.
- Authors: Rosen EY, Johnson ML, Clifford SE, Somwar R, Kherani JF, Son J, Bertram AA, Davare MA, Gladstone E, Ivanova EV, Henry DN, Kelley EM, Lin M, Milan MSD, Nair BC, Olek EA, Scanlon JE, Vojnic M, Ebata K, Hechtman JF, Li BT, Sholl LM, Taylor BS, Ladanyi M, Jänne PA, Rothenberg SM, Drilon A, Oxnard GR
- Issue date: 2021 Jan 1
- Efficacy of Selpercatinib in <i>RET</i> Fusion-Positive Non-Small-Cell Lung Cancer.
- Authors: Drilon A, Oxnard GR, Tan DSW, Loong HHF, Johnson M, Gainor J, McCoach CE, Gautschi O, Besse B, Cho BC, Peled N, Weiss J, Kim YJ, Ohe Y, Nishio M, Park K, Patel J, Seto T, Sakamoto T, Rosen E, Shah MH, Barlesi F, Cassier PA, Bazhenova L, De Braud F, Garralda E, Velcheti V, Satouchi M, Ohashi K, Pennell NA, Reckamp KL, Dy GK, Wolf J, Solomon B, Falchook G, Ebata K, Nguyen M, Nair B, Zhu EY, Yang L, Huang X, Olek E, Rothenberg SM, Goto K, Subbiah V
- Issue date: 2020 Aug 27
- Selpercatinib in RET fusion-positive non-small-cell lung cancer (SIREN): a retrospective analysis of patients treated through an access program.
- Authors: Illini O, Hochmair MJ, Fabikan H, Weinlinger C, Tufman A, Swalduz A, Lamberg K, Hashemi SMS, Huemer F, Vikström A, Wermke M, Absenger G, Addeo A, Banerji S, Calles A, Clarke S, Di Maio M, Durand A, Duruisseaux M, Itchins M, Kääränien OS, Krenn F, Laack E, de Langen AJ, Mohorcic K, Pall G, Passaro A, Prager G, Rittmeyer A, Rothenstein J, Schumacher M, Wöll E, Valipour A
- Issue date: 2021