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    Tipifarnib in recurrent, metastatic HRAS-mutant salivary gland cancer

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    Authors
    Hanna, GJ
    Guenette, 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
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    Affiliation
    Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
    Issue Date
    2020
    
    Metadata
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    Abstract
    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
    Cancer
    URI
    http://hdl.handle.net/10541/623088
    DOI
    10.1002/cncr.33036
    PubMed ID
    32557577
    Additional Links
    https://dx.doi.org/10.1002/cncr.33036
    Type
    Article
    Language
    en
    ae974a485f413a2113503eed53cd6c53
    10.1002/cncr.33036
    Scopus Count
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