Characterization and Management of ERK Inhibitor Associated Dermatologic Adverse Events: Analysis from a Nonrandomized Trial of Ulixertinib for Advanced Cancers
| Autor: | D. Welsch, David M. Hyman, Cecilia Lezcano, Mary Varterasian, Ryan J. Sullivan, Mario E. Lacouture, Bob T. Li, Michael Offin, Dazhi Liu, Jean Torrisi, S. Brownstein, A. Groover, James J. Harding, J. Wu, Mrinal M. Gounder, Alexander Drilon, Filip Janku, W. Abida |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Oncology Adult Male medicine.medical_specialty Aminopyridines Antineoplastic Agents Article 03 medical and health sciences Young Adult 0302 clinical medicine Quality of life Internal medicine Neoplasms Maculopapular rash medicine Humans Pharmacology (medical) Pyrroles Adverse effect Extracellular Signal-Regulated MAP Kinases Protein Kinase Inhibitors Aged Skin Pharmacology Aged 80 and over Analgesics Surrogate endpoint business.industry Incidence (epidemiology) Middle Aged Rash Anti-Bacterial Agents Clinical trial 030104 developmental biology 030220 oncology & carcinogenesis Cohort Female Steroids Drug Eruptions medicine.symptom business |
| Zdroj: | Invest New Drugs |
| Popis: | Background Ulixertinib is the first-in-class ERK1/2 kinase inhibitor with encouraging clinical activity in BRAF- and NRAS-mutant cancers. Dermatologic adverse events (dAEs) are common with ulixertinib, so management guidelines like those established for epidermal growth factor receptor inhibitor (EGFRi)-associated dAEs are needed. Patients and Methods This was an open-label, multicenter, phase I dose escalation and expansion trial of ulixertinib evaluating data from 135 patients with advanced malignancies enrolled between March 2013 and July 2017. Histopathological features, management, and dAEs in 34 patients are also reported. Twice daily oral ulixertinib was administered at 10 to 900 mg in the dose escalation cohort (n = 27) and at 600 mg in 21-day cycles in the expansion cohort (n = 108). Results The incidence of ulixertinib-induced dAEs and combined rash were 79% (107/135) and 76% (102/135). The most common dAEs included acneiform rash (45/135, 33%), maculopapular rash (36/135, 27%), and pruritus (34/135, 25%). Grade 3 dAEs were observed in 19% (25/135) of patients; no grade 4 or 5 dAEs were seen. The presence of at least 1 dAE was associated with stable disease (SD) or partial response (PR) (OR = 3.64, 95% CI 1.52–8.72; P = .003). Acneiform rash was associated with a PR (OR = 10.19, 95% CI 2.67–38.91; P |
| Databáze: | OpenAIRE |
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