Characterization and management of ERK inhibitor associated dermatologic adverse events: Analysis from a nonrandomized trial of ulixertinib for advanced cancers Journal Article
| Authors: | Wu, J.; Liu, D.; Offin, M.; Lezcano, C.; Torrisi, J. M.; Brownstein, S.; Hyman, D. M.; Gounder, M. M.; Abida, W.; Drilon, A.; Harding, J. J.; Sullivan, R. J.; Janku, F.; Welsch, D.; Varterasian, M.; Groover, A.; Li, B. T.; Lacouture, M. E. |
| Article Title: | Characterization and management of ERK inhibitor associated dermatologic adverse events: Analysis from a nonrandomized trial of ulixertinib for advanced cancers |
| Abstract: | 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 <.001). Conclusion The clinical spectrum of ulixertinib-induced dAEs was similar to EGFR and MEK inhibitors; dAEs may serve as a surrogate marker of tumor response. We propose treatment algorithms for common ERK inhibitor-induced dAEs to maintain patients’ quality of life and dose intensity for maximal clinical benefit. Clinical Trial Registration: NCT01781429. © 2021, Springer Science+Business Media, LLC, part of Springer Nature. |
| Keywords: | adult; treatment outcome; aged; major clinical study; clinical trial; histopathology; advanced cancer; dose response; drug efficacy; incidence; cohort analysis; drug effect; risk factor; drug dose escalation; pruritus; rash; maculopapular rash; adverse outcome; multicenter study; erythema; open study; skin disease; dermatitis; clinical effectiveness; phase 1 clinical trial; trend study; dry skin; alopecia; photosensitivity; acneiform rash; dermatologic adverse events; human; male; female; priority journal; article; ulixertinib; erk inhibitor |
| Journal Title: | Investigational New Drugs |
| Volume: | 39 |
| Issue: | 3 |
| ISSN: | 0167-6997 |
| Publisher: | Springer |
| Date Published: | 2021-06-01 |
| Start Page: | 785 |
| End Page: | 795 |
| Language: | English |
| DOI: | 10.1007/s10637-020-01035-9 |
| PUBMED: | 33389388 |
| PROVIDER: | scopus |
| PMCID: | PMC9282166 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 June 2021 -- Source: Scopus |
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