Tipifarnib in recurrent, metastatic HRAS-mutant salivary gland cancer
Authors
Hanna, GJGuenette, JP
Chau, NG
Sayehli, CM
Wilhelm, C
Metcalf, Robert
Wong, DJ
Brose, M
Razaq, M
Perez-Ruiz, E
Cohen, EEW
Aggarwal, R
Scholz, C
Gualberto, A
Ho, AL
Affiliation
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.Issue Date
2020
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Background: To the authors' knowledge, there are no approved therapies for recurrent, metastatic (R/M) salivary gland carcinoma (SGC), but molecularly targeted therapies warrant ongoing investigation. In the current study, the authors have reported on the efficacy of tipifarnib in patients with aggressive HRAS-mutant, R/M SGC. Methods: The current prospective, nonrandomized, multicenter, international cohort study involved 8 centers and was conducted from May 2015 to June 2019. The median follow-up was 22 months (range, 6-55 months). Subjects with HRAS-mutant R/M SGC (any histology) and disease progression within the last 6 months were enrolled. Tipifarnib was dosed orally twice daily. The authors determined the objective response rate using Response Evaluation Criteria in Solid Tumors (version 1.1), duration of response, and molecular predictors of response. Results: A total of 13 patients with R/M SGC were enrolled; all had received prior systemic therapy (1-3 regimens). One objective response was observed; an additional 7 of 12 evaluable patients (58%) had stable disease as their best response with a median duration of 9 months (range, 3-14 months). Five of 7 patients had >10% tumor regression and 6 of 7 had stable disease lasting >6 months. Q61R was the most frequent activating HRAS mutation noted (7 of 13 patients; 54%), but gene variant and allele frequency did not correlate with outcomes. The median progression-free survival was 7 months (95% confidence interval, 5.9-10.1 months), and the median overall survival was 18 months (95% confidence interval, 9.6-22.4 months) with approximately 58.6% of patients alive at 1 year. Survival was similar regardless of HRAS mutant variant or co-occurring PIK3CA alterations. No participant discontinued treatment because of toxicity. Conclusions: Tipifarnib resulted in modest clinical activity with a promising disease control rate among patients with HRAS-mutant, R/M SGC who developed disease progression within the last 6 months. Keywords: HRAS; rare cancers; salivary cancer; targeted therapy; tipifarnib.Citation
Hanna GJ, Guenette JP, Chau NG, Sayehli CM, Wilhelm C, Metcalf R, et al. Tipifarnib in recurrent, metastatic HRAS-mutant salivary gland cancer. Cancer. 2020.Journal
CancerDOI
10.1002/cncr.33036PubMed ID
32557577Additional Links
https://dx.doi.org/10.1002/cncr.33036Type
ArticleLanguage
enae974a485f413a2113503eed53cd6c53
10.1002/cncr.33036
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