Mucocutaneous Adverse Events in Patients With Cancer Treated with the Highly Selective RET Kinase Inhibitor Selpercatinib (LOXO-292)

Rachel E. Reingold, MD; Rose Parisi, MD, MBA; Guilherme Harada, MD; Andrea P. Moy, MD; George Dranitsaris, PhD; Jasmine H. Francis, MD; Julia Canestraro, OD, FAAO; Julia A. Lester, MPH; Lauren A. Kaplanis, RN; Dazhi Liu, PharmD, BCOP; Mario E. Lacouture, MD; Alexander Drilon, MD

JTO Clinical and Research Reports (Mar 2025)

Mucocutaneous Adverse Events in Patients With Cancer Treated with the Highly Selective RET Kinase Inhibitor Selpercatinib (LOXO-292)

Rachel E. Reingold, MD,
Rose Parisi, MD, MBA,
Guilherme Harada, MD,
Andrea P. Moy, MD,
George Dranitsaris, PhD,
Jasmine H. Francis, MD,
Julia Canestraro, OD, FAAO,
Julia A. Lester, MPH,
Lauren A. Kaplanis, RN,
Dazhi Liu, PharmD, BCOP,
Mario E. Lacouture, MD,
Alexander Drilon, MD

Affiliations

Rachel E. Reingold, MD: Dermatology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York; Department of Dermatology, Weill Cornell Medical College, New York, New York
Rose Parisi, MD, MBA: Dermatology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York
Guilherme Harada, MD: Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York; Early Drug Development Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York
Andrea P. Moy, MD: Dermatopathology Service, Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York
George Dranitsaris, PhD: Department of Public Health, Falk College, Syracuse University, Syracuse, New York
Jasmine H. Francis, MD: Ophthalmic Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York
Julia Canestraro, OD, FAAO: Ophthalmic Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York
Julia A. Lester, MPH: Ophthalmic Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York
Lauren A. Kaplanis, RN: Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York; Early Drug Development Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York
Dazhi Liu, PharmD, BCOP: Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York; Early Drug Development Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York
Mario E. Lacouture, MD: Dermatology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York; Department of Dermatology, Weill Cornell Medical College, New York, New York
Alexander Drilon, MD: Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York; Early Drug Development Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York; Department of Medicine, Weill Cornell Medical College, New York, New York; Corresponding author: Address for correspondence: Alexander Drilon, MD, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, 530 E 74th St, New York 10021, New York.

Journal volume & issue: Vol. 6, no. 3
p. 100792

Abstract

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Introduction: Selective RET inhibitors are approved for the treatment of RET-dependent cancers. A comprehensive characterization of mucocutaneous adverse events (MAEs) has not been performed; therefore, we characterized MAEs associated with the selective RET inhibitor, selpercatinib. Methods: We assessed 133 patients with RET-altered cancers treated with selpercatinib. The type, grade, cumulative incidence, and time to onset of MAEs were determined. Therapy interruptions, clinicopathologic findings, and management were described. Laboratory values were compared between patients with and without MAEs. Results: A total of 73 patients with mostly NSCLC (n = 46, 63%), medullary thyroid (n = 19, 26%), and papillary thyroid (n = 6, 8%) cancers had 126 predominantly grade 1/2 (n = 124, 98%) MAEs, with 48% reporting greater than one MAE. Xerostomia (n = 49, 37%), rash (n = 24, 18%), periorbital edema (n = 16, 12%), and xerosis (n = 12, 9%) were the most common MAEs. The yearly cumulative incidence of all-grade MAEs was 55%, with a median time to onset of 57 (interquartile range: 15–166) days after initiation. Those with MAEs had a significantly higher percentage of lymphocytes (mean = 21.8, SD = 11.3, p = 0.005) compared with those without MAEs (16.9, SD = 10.0) and elevated immunoglobulin E (mean = 275, SD = 294.5 IU/mL). There were 18 (14%) MAE-related therapy interruptions, including the following: three (2%) rechallenged with dose maintained, 10 (7%) with a 50% dose reduction, 5 (4%) with a 25% dose reduction, and no drug discontinuations. A treatment algorithm was created for the most common MAEs: xerostomia managed with saliva and lubricants; mucositis with steroid rinses; rashes with topical steroids with or without topical ammonium lactate; periorbital edema with cold or caffeine compresses; and xerosis and pruritus with emollients. Conclusions: Selective RET inhibition is associated with a unique MAE profile. Early recognition and management of MAEs may improve quality of life, minimize interruptions, and maximize therapeutic benefit.

Published in JTO Clinical and Research Reports

ISSN: 2666-3643 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Internal medicine: Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Website: https://www.journals.elsevier.com/jto-clinical-and-research-reports/

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