Tipifarnib in recurrent, metastatic HRAS-mutant salivary gland cancer

被引：39

作者：

Hanna, Glenn J. ^{[1
]}

Guenette, Jeffrey P. ^{[2
]}

Chau, Nicole G. ^{[3
]}

Sayehli, Cyrus M. ^{[4
]}

Wilhelm, Christian ^{[5
]}

Metcalf, Robert ^{[6
]}

Wong, Deborah J. ^{[7
]}

Brose, Marcia ^{[8
]}

Razaq, Mohammad ^{[9
]}

Perez-Ruiz, Elisabeth ^{[10
]}

Cohen, Ezra E. W. ^{[11
]}

Aggarwal, Rahul ^{[12
]}

Scholz, Catherine ^{[13
]}

Gualberto, Antonio ^{[13
]}

Ho, Alan L. ^{[14
,15
]}

机构：

[1] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA

[2] Brigham & Womens Hosp, Dana Farber Canc Inst, Div Neuroradiol, 75 Francis St, Boston, MA 02115 USA

[3] BC Canc Vancouver Ctr, Dept Med Oncol, Vancouver, BC, Canada

[4] Univ Hosp Wurzburg, Dept Internal Med 2, Early Clin Trial Unit, Wurzburg, Germany

[5] Julius Maximilian Univ Wuerzburg, Dept Otorhinolaryngol Plast Aesthet & Reconstruct, Wurzburg, Germany

[6] Christie NHS Fdn Trust, Med Oncol, Manchester, Lancs, England

[7] Ronald Reagan Univ Calif Los Angeles, Div Hematol & Oncol, Dept Med, Med Ctr, Los Angeles, CA USA

[8] Hosp Univ Penn, Dept Otorhinolaryngol Head & Neck Surg, 3400 Spruce St, Philadelphia, PA 19104 USA

[9] Univ Oklahoma, Dept Hematol Oncol, Stephenson Canc Ctr, Oklahoma City, OK USA

[10] Costa Sol Hlth Agcy, Dept Med Oncol, Inst Biomed Res Malaga, Marbella, Spain

[11] Univ Calif San Diego Hlth, Moores Canc Ctr, Div Hematol Oncol, San Diego, CA USA

[12] Univ Calif San Francisco, Div Hematol Oncol, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA

[13] Kura Oncol, San Diego, CA USA

[14] Mem Sloan Kettering Canc Ctr, Dept Hematol Oncol, 1275 York Ave, New York, NY 10065 USA

[15] Weill Cornell Med Coll, Dept Med, New York, NY USA

来源：

CANCER | 2020年 / 126卷 / 17期

关键词：

HRAS; rare cancers; salivary cancer; targeted therapy; tipifarnib; PHASE-II; DUCT CARCINOMA; RAS; LANDSCAPE; TUMORS;

D O I：

10.1002/cncr.33036

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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 aggressiveHRAS-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 withHRAS-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 activatingHRASmutation 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 ofHRASmutant variant or co-occurringPIK3CAalterations. No participant discontinued treatment because of toxicity. Conclusions Tipifarnib resulted in modest clinical activity with a promising disease control rate among patients withHRAS-mutant, R/M SGC who developed disease progression within the last 6 months.

引用

页码：3972 / 3981

页数：10

共 31 条

[1] Phase II study of lapatinib in recurrent or metastatic epidermal growth factor receptor and/or erbB2 expressing adenoid cystic carcinoma and non-adenoid cystic carcinoma malignant tumors of the salivary glands [J].

Agulnik, Mark ;

Cohen, Ezra W. E. ;

Cohen, Roger B. ;

Chen, Eric X. ;

Vokes, Everett E. ;

Hotte, Sebastien J. ;

Winquist, Eric ;

Laurie, Scott ;

Hayes, D. Neil ;

Dancey, Janet E. ;

Brown, Shirley ;

Pond, Gregory R. ;

Lorimer, Ian ;

Daneshmand, Manijeh ;

Ho, James ;

Tsao, Ming-Sound ;

Siu, Lillian L. .

JOURNAL OF CLINICAL ONCOLOGY, 2007, 25 (25) :3978-3984

[2] Association of Adjuvant Chemoradiotherapy vs Radiotherapy Alone With Survival in Patients With Resected Major Salivary Gland Carcinoma Data From the National Cancer Data Base [J].

Amini, Arya ;

Waxweiler, Timothy V. ;

Brower, Jeffrey V. ;

Jones, Bernard L. ;

McDermott, Jessica D. ;

Raben, David ;

Ghosh, Debashis ;

Bowles, Daniel W. ;

Karam, Sana D. .

JAMA OTOLARYNGOLOGY-HEAD & NECK SURGERY, 2016, 142 (11) :1100-1110

[3] The farnesyl transferase inhibitor SCH 66336 induces a G2 → M or G1 pause in sensitive human tumor cell lines [J].

Ashar, HR ;

James, L ;

Gray, K ;

Carr, D ;

McGuirk, M ;

Maxwell, E ;

Black, S ;

Armstrong, L ;

Doll, RJ ;

Taveras, AG ;

Bishop, WR ;

Kirschmeier, P .

EXPERIMENTAL CELL RESEARCH, 2001, 262 (01) :17-27

[4] Androgen deprivation therapy for androgen receptor-positive advanced salivary duct carcinoma: A nationwide case series of 35 patients in The Netherlands [J].

Boon, Eline ;

van Boxtel, Wim ;

Buter, Jan ;

de Jong, Robert J. Baatenburg ;

van Es, Robert J. J. ;

Bel, Miranda ;

Fiets, Edward ;

Oosting, Sjoukje F. ;

Slingerland, Marije ;

Hoeben, Ann ;

Tesselaar, Margot E. T. ;

Jonker, Marianne A. ;

Flucke, Uta E. ;

van der Graaf, Winette T. A. ;

van Herpen, Carla M. L. .

HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK, 2018, 40 (03) :605-613

[5] Transformation by HrasG12V is consistently associated with mutant allele copy gains and is reversed by farnesyl transferase inhibition [J].

Chen, X. ;

Makarewicz, J. M. ;

Knauf, J. A. ;

Johnson, L. K. ;

Fagin, J. A. .

ONCOGENE, 2014, 33 (47) :5442-5449

[6] Human epidermal growth factor receptor 2 (HER2) in salivary gland carcinomas [J].

Clauditz, Till Sebastian ;

Reiff, Maren ;

Gravert, Linn ;

Gnoss, Alexander ;

Tsourlakis, Maria-Christina ;

Muenscher, Adrian ;

Sauter, Guido ;

Bokemeyer, Carsten ;

Knecht, Rainald ;

Wilczak, Waldemar .

PATHOLOGY, 2011, 43 (05) :459-464

[7] Pembrolizumab for the Treatment of Advanced Salivary Gland Carcinoma Findings of the Phase 1b KEYNOTE-028 Study [J].

Cohen, Roger B. ;

Delord, Jean-Pierre ;

Doi, Toshihiko ;

Piha-Paul, Sarina A. ;

Liu, Stephen V. ;

Gilbert, Jill ;

Algazi, Alain P. ;

Damian, Silvia ;

Hong, Ruey-Long ;

Le Tourneau, Christophe ;

Day, Daphne ;

Varga, Andrea ;

Elez, Elena ;

Wallmark, John ;

Saraf, Sanatan ;

Thanigaimani, Pradeep ;

Cheng, Jonathan ;

Keam, Bhumsuk .

AMERICAN JOURNAL OF CLINICAL ONCOLOGY-CANCER CLINICAL TRIALS, 2018, 41 (11) :1083-1088

[8] Comprehensive Molecular Characterization of Salivary Duct Carcinoma Reveals Actionable Targets and Similarity to Apocrine Breast Cancer [J].

Dalin, Martin G. ;

Desrichard, Alexis ;

Katabi, Nora ;

Makarov, Vladimir ;

Walsh, Logan A. ;

Lee, Ken-Wing ;

Wang, Qingguo ;

Armenia, Joshua ;

West, Lyndsay ;

Dogan, Snjezana ;

Wang, Lu ;

Ramaswami, Deepa ;

Ho, Alan L. ;

Ganly, Ian ;

Solit, David B. ;

Berger, Michael F. ;

Schultz, Nikolaus D. ;

Reis-Filho, Jorge S. ;

Chan, Timothy A. ;

Morris, Luc G. T. .

CLINICAL CANCER RESEARCH, 2016, 22 (18) :4623-4633

[9] Efficacy of Larotrectinib in TRK Fusion-Positive Cancers in Adults and Children [J].

Drilon, A. ;

Laetsch, T. W. ;

Kummar, S. ;

DuBois, S. G. ;

Lassen, U. N. ;

Demetri, G. D. ;

Nathenson, M. ;

Doebele, R. C. ;

Farago, A. F. ;

Pappo, A. S. ;

Turpin, B. ;

Dowlati, A. ;

Brose, M. S. ;

Mascarenhas, L. ;

Federman, N. ;

Berlin, J. ;

El-Deiry, W. S. ;

Baik, C. ;

Deeken, J. ;

Boni, V. ;

Nagasubramanian, R. ;

Taylor, M. ;

Rudzinski, E. R. ;

Meric-Bernstam, F. ;

Sohal, D. P. S. ;

Ma, P. C. ;

Raez, L. E. ;

Hechtman, J. F. ;

Benayed, R. ;

Ladanyi, M. ;

Tuch, B. B. ;

Ebata, K. ;

Cruickshank, S. ;

Ku, N. C. ;

Cox, M. C. ;

Hawkins, D. S. ;

Hong, D. S. ;

Hyman, D. M. .

NEW ENGLAND JOURNAL OF MEDICINE, 2018, 378 (08) :731-739

[10] New response evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1) [J].

Eisenhauer, E. A. ;

Therasse, P. ;

Bogaerts, J. ;

Schwartz, L. H. ;

Sargent, D. ;

Ford, R. ;

Dancey, J. ;

Arbuck, S. ;

Gwyther, S. ;

Mooney, M. ;

Rubinstein, L. ;

Shankar, L. ;

Dodd, L. ;

Kaplan, R. ;

Lacombe, D. ;

Verweij, J. .

EUROPEAN JOURNAL OF CANCER, 2009, 45 (02) :228-247

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