The efficacy of tucatinib-based therapeutic approaches for HER2-positive breast cancer

Zaid Sirhan; Anita Thyagarajan; Ravi P. Sahu

doi:10.1186/s40779-022-00401-3

Your Location：

Home >

Browse articles >

The efficacy of tucatinib-based therapeutic approaches for HER2-positive breast cancer

REVIEW | Updated：2023-02-28

- The efficacy of tucatinib-based therapeutic approaches for HER2-positive breast cancer
- The efficacy of tucatinib-based therapeutic approaches for HER2-positive breast cancer
- 解放军医学杂志（英文版） 2022年9卷第5期页码：628-636
- Affiliations：
  
  Department of Pharmacology and Toxicology, Boonshoft School of Medicine Wright State University, Dayton, OH 45435, USA
- Author bio：
  
  * ravi.sahu@wright.edu
- Funds：
- DOI：10.1186/s40779-022-00401-3
  中图分类号：
- 纸质出版：2022-10
- Accepted：
Scan QR Code
The efficacy of tucatinib-based therapeutic approaches for HER2-positive breast cancer[J]. 解放军医学杂志（英文版）, 2022,9(5):628-636.

Sirhan Z, Thyagarajan A, Sahu RP. The efficacy of tucatinib-based therapeutic approaches for HER2-positive breast cancer. Mil Med Res. 2022;9(1):39.
The efficacy of tucatinib-based therapeutic approaches for HER2-positive breast cancer[J]. 解放军医学杂志（英文版）, 2022,9(5):628-636. DOI： 10.1186/s40779-022-00401-3.

Sirhan Z, Thyagarajan A, Sahu RP. The efficacy of tucatinib-based therapeutic approaches for HER2-positive breast cancer. Mil Med Res. 2022;9(1):39. DOI： 10.1186/s40779-022-00401-3.

摘要

Abstract

Overexpression of human epidermal growth factor receptor 2 (HER2) occurs in approximately 15%–20% of breast cancer cases. HER2 is a member of the epidermal growth factor receptor (EGFR) family with tyrosinase kinase activity

and its overexpression is linked to poor prognosis and shorter progression-free survival (PFS) and overall survival (OS). Among various treatment options

HER2-targeting monoclonal antibodies and tyrosine kinase inhibitors (TKIs) have mostly been applied in recent decades to treat HER2-positive (HER2

) breast cancer patients. Although positive clinical outcomes were documented in both advanced disease and neoadjuvant settings

the development of resistance mechanisms to such approaches has been one of the major challenges with the continuous usage of these drugs. In addition

patients who experience disease progression after treatment with multiple HER2-targeted therapies often have limited treatment options. The Food and Drug Administration (FDA) has recently approved a new TKI (i.e.

tucatinib) for use in combination with immunotherapy and/or chemotherapeutic agents for the treatment of advanced-stage/metastatic HER2

breast cancer. This review highlights recent updates on the efficacy of tucatinib-based therapeutic approaches in experimental models as well as in the clinical settings of HER2

breast cancer.

关键词

Keywords

references

DeSantis CE , Ma J , Gaudet MM , Newman LA , Miller KD , Goding Sauer A , et al . Breast cancer statistics, 2019 . CA Cancer J Clin . 2019 ; 69 ( 6 ): 438 - 51 .

Siegel RL , Miller KD , Jemal A . Cancer statistics, 2020 . CA Cancer J Clin . 2020 ; 70 ( 1 ): 7 - 30 .

DeSantis CE , Miller KD , Goding Sauer A , Jemal A , Siegel RL . Cancer statistics for African Americans, 2019 . CA Cancer J Clin . 2019 ; 69 ( 3 ): 211 - 33 .

Feng Y , Spezia M , Huang S , Yuan C , Zeng Z , Zhang L , et al . Breast cancer development and progression: Risk factors, cancer stem cells, signaling pathways, genomics, and molecular pathogenesis . Genes Dis . 2018 ; 5 ( 2 ): 77 - 106 .

Yeo SK , Guan JL . Breast cancer: Multiple subtypes within a tumor? Trends Cancer . 2017 ; 3 ( 11 ): 753 - 60 .

Harbeck N , Gnant M . Breast cancer . Lancet . 2017 ; 389 ( 10074 ): 1134 - 50 .

Howlader N , Cronin KA , Kurian AW , Andridge R . Differences in breast cancer survival by molecular subtypes in the United States . Cancer Epidemiol Biomark Prev . 2018 ; 27 ( 6 ): 619 - 26 .

Dai X , Li T , Bai Z , Yang Y , Liu X , Zhan J , et al . Breast cancer intrinsic subtype classification, clinical use and future trends . Am J Cancer Res . 2015 ; 5 ( 10 ): 2929 - 43 .

Huszno J , Nowara E . Risk factors for disease progression in HER2-positive breast cancer patients based on the location of metastases . Prz Menopauzalny . 2015 ; 14 ( 3 ): 173 - 7 .

Barnard ME , Boeke CE , Tamimi RM . Established breast cancer risk factors and risk of intrinsic tumor subtypes . Biochim Biophys Acta . 2015 ; 1856 ( 1 ): 73 - 85 .

Hamajima N , Hirose K , Tajima K , Rohan T , Calle EE , Heath CWJ , et al . Alcohol, tobacco and breast cancer–collaborative reanalysis of individual data from 53 epidemiological studies, including 58,515 women with breast cancer and 95,067 women without the disease . Br J Cancer . 2002 ; 87 ( 11 ): 1234 - 45 .

Jung S , Wang M , Anderson K , Baglietto L , Bergkvist L , Bernstein L , et al . Alcohol consumption and breast cancer risk by estrogen receptor status: in a pooled analysis of 20 studies . Int J Epidemiol . 2016 ; 45 ( 3 ): 916 - 28 .

Makarem N , Chandran U , Bandera EV , Parekh N . Dietary fat in breast cancer survival . Annu Rev Nutr . 2013 ; 33 : 319 - 48 .

Catsburg C , Miller AB , Rohan TE . Active cigarette smoking and risk of breast cancer . Int J Cancer . 2015 ; 136 ( 9 ): 2204 - 9 .

Gaudet MM , Carter BD , Brinton LA , Falk RT , Gram IT , Luo J , et al . Pooled analysis of active cigarette smoking and invasive breast cancer risk in 14 cohort studies . Int J Epidemiol . 2017 ; 46 ( 3 ): 881 - 93 .

Di Fiore PP , Pierce JH , Kraus MH , Segatto O , King CR , Aaronson SA . erbB-2 is a potent oncogene when overexpressed in NIH/3T3 cells . Science . 1987 ; 237 ( 4811 ): 178 - 82 .

Muller WJ , Sinn E , Pattengale PK , Wallace R , Leder P . Single-step induction of mammary adenocarcinoma in transgenic mice bearing the activated c-neu oncogene . Cell . 1988 ; 54 ( 1 ): 105 - 15 .

Du Z , Lovly CM . Mechanisms of receptor tyrosine kinase activation in cancer . Mol Cancer . 2018 ; 17 ( 1 ): 58 .

Dittrich A , Gautrey H , Browell D , Tyson-Capper A . The HER2 signaling network in breast cancer-like a spider in its web . J Mammary Gland Biol Neoplasia . 2014 ; 19 ( 3–4 ): 253 - 70 .

Bredin P , Walshe JM , Denduluri N . Systemic therapy for metastatic HER2-positive breast cancer . Semin Oncol . 2020 ; 47 ( 5 ): 259 - 69 .

Gajria D , Chandarlapaty S . HER2-amplified breast cancer: mechanisms of trastuzumab resistance and novel targeted therapies . Expert Rev Anticancer Ther . 2011 ; 11 ( 2 ): 263 - 75 .

Nami B , Maadi H , Wang Z . Mechanisms underlying the action and synergism of trastuzumab and pertuzumab in targeting HER2-positive breast cancer . Cancers (Basel) . 2018 ; 10 ( 10 ): 342 .

Hubbard SR , Till JH . Protein tyrosine kinase structure and function . Annu Rev Biochem . 2000 ; 69 : 373 - 98 .

Freudenberg JA , Wang Q , Katsumata M , Drebin J , Nagatomo I , Greene MI . The role of HER2 in early breast cancer metastasis and the origins of resistance to HER2-targeted therapies . Exp Mol Pathol . 2009 ; 87 ( 1 ): 1 - 11 .

Cronin KA , Harlan LC , Dodd KW , Abrams JS , Ballard-Barbash R . Populationbased estimate of the prevalence of HER-2 positive breast cancer tumors for early stage patients in the US . Cancer Invest . 2010 ; 28 ( 9 ): 963 - 8 .

Hsu JL , Hung MC . The role of HER2, EGFR, and other receptor tyrosine kinases in breast cancer . Cancer Metastasis Rev . 2016 ; 35 ( 4 ): 575 - 88 .

Masuda N , Lee SJ , Ohtani S , Im YH , Lee ES , Yokota I , et al . Adjuvant capecitabine for breast cancer after preoperative chemotherapy . N Engl J Med . 2017 ; 376 ( 22 ): 2147 - 59 .

Nakatsukasa K , Koyama H , Oouchi Y , Imanishi S , Mizuta N , Sakaguchi K , et al . Docetaxel and cyclophosphamide as neoadjuvant chemotherapy in HER2-negative primary breast cancer . Breast Cancer . 2017 ; 24 ( 1 ): 63 - 8 .

Ferguson T , Wilcken N , Vagg R , Ghersi D , Nowak AK . Taxanes for adjuvant treatment of early breast cancer . Cochrane database Syst Rev . 2007 ; 4 : CD004421 .

Nabholtz JM , Gligorov J . Docetaxel in the treatment of breast cancer: current experience and future prospects . Expert Rev Anticancer Ther . 2005 ; 5 ( 4 ): 613 - 33 .

File D , Curigliano G , Carey LA . Escalating and de-escalating therapy for early-stage HER2-positive breast Cancer . Am Soc Clin Oncol Educ Book . 2020 ; 40 : 1 - 11 .

Kreutzfeldt J , Rozeboom B , Dey N , De P . The trastuzumab era: current and upcoming targeted HER2+ breast cancer therapies . Am J Cancer Res . 2020 ; 10 ( 4 ): 1045 - 67 .

Murthy RK , Loi S , Okines A , Paplomata E , Hamilton E , Hurvitz SA , et al . Tucatinib, trastuzumab, and capecitabine for HER2-positive metastatic breast cancer . N Engl J Med . 2020 ; 382 ( 7 ): 597 - 609 .

Duchnowska R , Loibl S , Jassem J . Tyrosine kinase inhibitors for brain metastases in HER2-positive breast cancer . Cancer Treat Rev . 2018 ; 67 : 71 - 7 .

Piccart-Gebhart MJ , Procter M , Leyland-Jones B , Goldhirsch A , Untch M , Smith I , et al . Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer . N Engl J Med . 2005 ; 353 ( 16 ): 1659 - 72 .

Figueroa-Magalhães MC , Jelovac D , Connolly R , Wolff AC . Treatment of HER2-positive breast cancer . Breast . 2014 ; 23 ( 2 ): 128 - 36 .

Swain SM , Miles D , Kim SB , Im YH , Im SA , Semiglazov V , et al . Pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer (CLEOPATRA): end-of-study results from a double-blind, randomised, placebo-controlled, phase 3 study . Lancet Oncol . 2020 ; 21 ( 4 ): 519 - 30 .

Cesca MG , Vian L , Cristóvão-Ferreira S , Pondé N , de Azambuja E . HER2-positive advanced breast cancer treatment in 2020 . Cancer Treat Rev . 2020 ; 88 : 102033 .

Tesch ME , Gelmon KA . Targeting HER2 in Breast Cancer: Latest developments on treatment sequencing and the introduction of biosimilars . Drugs . 2020 ; 80 ( 17 ): 1811 - 30 .

Santa-Maria CA , Nye L , Mutonga MB , Jain S , Gradishar WJ . Management of metastatic HER2-positive breast cancer: Where are we and where do we go from here? Oncology . 2016 ; 30 ( 2 ): 148 - 55 .

Xuhong JC , Qi XW , Zhang Y , Jiang J . Mechanism, safety and efficacy of three tyrosine kinase inhibitors lapatinib, neratinib and pyrotinib in HER2-positive breast cancer . Am J Cancer Res . 2019 ; 9 ( 10 ): 2103 - 19 .

Schlam I , Swain SM . HER2-positive breast cancer and tyrosine kinase inhibitors: the time is now . NPJ Breast Cancer . 2021 ; 7 ( 1 ): 56 .

Yang X , Wu D , Yuan S . Tyrosine kinase inhibitors in the combination therapy of HER2 positive breast cancer . Technol Cancer Res Treat . 2020 ; 19 : 1533033820962140 .

Barok M , Joensuu H , Isola J . Trastuzumab emtansine: mechanisms of action and drug resistance . Breast Cancer Res . 2014 ; 16 ( 2 ): 209 .

Krasniqi E , Barchiesi G , Pizzuti L , Mazzotta M , Venuti A , Maugeri-Saccà M , et al . Immunotherapy in HER2-positive breast cancer: state of the art and future perspectives . J Hematol Oncol . 2019 ; 12 ( 1 ): 111 .

Murthy R , Borges VF , Conlin A , Chaves J , Chamberlain M , Gray T , et al . Tucatinib with capecitabine and trastuzumab in advanced HER2-positive metastatic breast cancer with and without brain metastases: a nonrandomised, open-label, phase 1b study . Lancet Oncol . 2018 ; 19 ( 7 ): 880 - 8 .

Lin NU , Borges V , Anders C , Murthy RK , Paplomata E , Hamilton E , et al . Intracranial efficacy and survival with tucatinib plus trastuzumab and capecitabine for previously treated HER2-positive breast cancer with brain metastases in the HER2CLIMB trial . J Clin Oncol . 2020 ; 38 ( 23 ): 2610 - 9 .

Cuello M , Ettenberg SA , Clark AS , Keane MM , Posner RH , Nau MM , et al . Down-regulation of the erbB-2 receptor by trastuzumab (herceptin) enhances tumor necrosis factor-related apoptosis-inducing ligand-mediated apoptosis in breast and ovarian cancer cell lines that overexpress erbB-2 . Cancer Res . 2001 ; 61 ( 12 ): 4892 - 900 .

Junttila TT , Akita RW , Parsons K , Fields C , Lewis Phillips GD , Friedman LS , et al . Ligand-independent HER2/HER3/PI3K complex is disrupted by trastuzumab and is effectively inhibited by the PI3K inhibitor GDC-0941 . Cancer Cell . 2009 ; 15 ( 5 ): 429 - 40 .

Molina MA , Codony-Servat J , Albanell J , Rojo F , Arribas J , Baselga J . Trastuzumab (herceptin), a humanized anti-Her2 receptor monoclonal antibody, inhibits basal and activated Her2 ectodomain cleavage in breast cancer cells . Cancer Res . 2001 ; 61 ( 12 ): 4744 - 9 .

Varchetta S , Gibelli N , Oliviero B , Nardini E , Gennari R , Gatti G , et al . Elements related to heterogeneity of antibody-dependent cell cytotoxicity in patients under trastuzumab therapy for primary operable breast cancer overexpressing Her2 . Cancer Res . 2007 ; 67 ( 24 ): 11991 - 9 .

Nahta R , Takahashi T , Ueno NT , Hung MC , Esteva FJ . P27(kip1) down-regulation is associated with trastuzumab resistance in breast cancer cells . Cancer Res . 2004 ; 64 ( 11 ): 3981 - 6 .

Zhang H , Berezov A , Wang Q , Zhang G , Drebin J , Murali R , et al . ErbB receptors: from oncogenes to targeted cancer therapies . J Clin Invest . 2007 ; 117 ( 8 ): 2051 - 8 .

Hennessy BT , Smith DL , Ram PT , Lu Y , Mills GB . Exploiting the PI3K/AKT pathway for cancer drug discovery . Nat Rev Drug Discov . 2005 ; 4 ( 12 ): 988 - 1004 .

Derakhshani A , Rezaei Z , Safarpour H , Sabri M , Mir A , Sanati MA , et al . Overcoming trastuzumab resistance in HER2-positive breast cancer using combination therapy . J Cell Physiol . 2020 ; 235 ( 4 ): 3142 - 56 .

Brandão M , Pondé NF , Poggio F , Kotecki N , Salis M , Lambertini M , et al . Combination therapies for the treatment of HER2-positive breast cancer: current and future prospects . Expert Rev Anticancer Ther . 2018 ; 18 ( 7 ): 629 - 49 .

Paplomata E , O’Regan R . The PI3K/AKT/mTOR pathway in breast cancer: targets, trials and biomarkers . Ther Adv Med Oncol . 2014 ; 6 ( 4 ): 154 - 66 .

Luque-Cabal M , García-Teijido P , Fernández-Pérez Y , Sánchez-Lorenzo L , Palacio-Vázquez I . Mechanisms behind the resistance to trastuzumab in HER2-amplified breast cancer and strategies to overcome it . Clin Med Insights Oncol . 2016 ; 10 ( Suppl 1 ): 21 - 30 .

Maier LA , Xu FJ , Hester S , Boyer CM , McKenzie S , Bruskin AM , et al . Requirements for the internalization of a murine monoclonal antibody directed against the HER-2/neu gene product C-ERBB-2 . Cancer Res . 1991 ; 51 ( 19 ): 5361 - 9 .

Nagata Y , Lan KH , Zhou X , Tan M , Esteva FJ , Sahin AA , et al . PTEN activation contributes to tumor inhibition by trastuzumab, and loss of PTEN predicts trastuzumab resistance in patients . Cancer Cell . 2004 ; 6 ( 2 ): 117 - 27 .

Scaltriti M , Rojo F , Ocaña A , Anido J , Guzman M , Cortes J , et al . Expression of p95HER2, a truncated form of the HER2 receptor, and response to anti- HER2 therapies in breast cancer . J Natl Cancer Inst . 2007 ; 99 ( 8 ): 628 - 38 .

Pereira PMR , Sharma SK , Carter LM , Edwards KJ , Pourat J , Ragupathi A , et al . Caveolin-1 mediates cellular distribution of HER2 and affects trastuzumab binding and therapeutic efficacy . Nat Commun . 2018 ; 9 ( 1 ): 5137 .

Pietilä M , Sahgal P , Peuhu E , Jäntti NZ , Paatero I , Närvä E , et al . SORLA regulates endosomal trafficking and oncogenic fitness of HER2 . Nat Commun . 2019 ; 10 ( 1 ): 2340 .

Li BT , Michelini F , Misale S , Cocco E , Baldino L , Cai Y , et al . HER2-mediated internalization of cytotoxic agents in ERBB2 amplified or mutant lung cancers . Cancer Discov . 2020 ; 10 ( 5 ): 674 - 87 .

Moulder SL , Borges VF , Baetz T , Mcspadden T , Fernetich G , Murthy RK , et al . Phase I study of ONT-380, a HER2 inhibitor, in patients with HER2 + -advanced solid tumors, with an expansion cohort in HER2 + metastatic breast cancer (MBC) . Clin Cancer Res . 2017 ; 23 ( 14 ): 3529 - 36 .

Borges VF , Ferrario C , Aucoin N , Falkson CI , Khan QJ , Krop IE , et al . Efficacy results of a phase 1b study of ONT-380, a CNS-penetrant TKI, in combination with T-DM1 in HER2 + metastatic breast cancer (MBC), including patients (pts) with brain metastases . J Clin Oncol . 2016 ; 34 ( Suppl 15 ): 513 .

Dinkel V , Anderson D , Winski S , Winkler J , Koch K , Lee PA . ARRY-380, a potent, small molecule inhibitor of ErbB2, increases survival in intracranial ErbB2 + xenograft models in mice . Cancer Res . 2012 ; 72 ( Suppl 8 ): 852 .

Vo AC , Walker L , Hausman D , Peterson S . Abstract B152: Clinical pharmacokinetics of an improved tablet formulation of ONT-380 in HER2 + metastatic breast cancer patients . Mol Cancer Ther . 2015 ; 14 ( 12 Supplement 2 ): B152 .

Kulukian A , Lee P , Taylor J , Rosler R , de Vries P , Watson D , et al . Preclinical activity of HER2-selective tyrosine kinase inhibitor tucatinib as a single agent or in combination with trastuzumab or docetaxel in solid tumor models . Mol Cancer Ther . 2020 ; 19 ( 4 ): 976 - 87 .

O’Sullivan CC , Davarpanah NN , Abraham J , Bates SE . Current challenges in the management of breast cancer brain metastases . Semin Oncol . 2017 ; 44 ( 2 ): 85 - 100 .

Kunte S , Abraham J , Montero AJ . Novel HER2-targeted therapies for HER2-positive metastatic breast cancer . Cancer . 2020 ; 126 ( 19 ): 4278 - 88 .

Kaur S , Bhattacharyya R , Banerjee D , Shukla J . Application of tucatinib and trastuzumab: dual anti HER2 therapy against HER2 positive breast cancer . Indian J Clin Biochem . 2021 ; 36 ( 1 ): 124 - 5 .

Hudis CA . Trastuzumab–mechanism of action and use in clinical practice . N Engl J Med . 2007 ; 357 ( 1 ): 39 - 51 .

Zhao J , Mohan N , Nussinov R , Ma B , Wu WJ . Trastuzumab blocks the receiver function of HER2 leading to the population shifts of HER2-containing homodimers and heterodimers . Antibodies . 2021 ; 10 ( 1 ): 7 .

Conlon NT , Kooijman JJ , van Gerwen SJC , Mulder WR , Zaman GJR , Diala I , et al . Comparative analysis of drug response and gene profiling of HER2-targeted tyrosine kinase inhibitors . Br J Cancer . 2021 ; 124 ( 7 ): 1249 - 59 .

Zimmer AS , Van Swearingen AED , Anders CK . HER2-positive breast cancer brain metastasis: a new and exciting landscape . Cancer Rep . 2022 ; 5 ( 4 ): e1274 .

Borges VF , Ferrario C , Aucoin N , Falkson C , Khan Q , Krop I , et al . Tucatinib combined with ado-trastuzumab emtansine in advanced ERBB2/HER2-positive metastatic breast cancer: a phase 1b clinical trial . JAMA Oncol . 2018 ; 4 ( 9 ): 1214 - 20 .

Metzger Filho O , Leone JP , Li T , Tan-Wasielewski Z , Trippa L , Barry WT , et al . Phase I dose-escalation trial of tucatinib in combination with trastuzumab in patients with HER2-positive breast cancer brain metastases . Ann Oncol . 2020 ; 31 ( 9 ): 1231 - 9 .

Murthy RK , O’Brien B , Berry DA , Singareeka-Raghavendra A , Monroe MG , Johnson J , et al . Abstract PD4-02: safety and efficacy of a tucatinib-trastuzumab-capecitabine regimen for treatment of leptomeningeal metastasis (LM) in HER2-positive breast cancer: Results from TBCRC049, a phase 2 non-randomized study . Cancer Res . 2022 ; 82 ( 4_Supplement ): PD4 - 02 .

Bartsch R . ASCO 2020: highlights in breast cancer . Memo . 2021 ; 14 ( 1 ): 58 - 61 .

Strickler JH , Ng K , Cercek A , Fountzilas C , Sanchez FA , Hubbard JM , et al . MOUNTAINEER: open-label, Phase II study of tucatinib combined with trastuzumab for HER2-positive metastatic colorectal cancer (SGNTUC-017, trial in progress) . J Clin Oncol . 2021 ; 39 ( Sppl 3 ): TPS153 .

Strickler JH , Nakamura Y , Yoshino T , Catenacci DVT , Janjigian YY , Barzi A , et al . MOUNTAINEER-02: Phase II/III study of tucatinib, trastuzumab, ramucirumab, and paclitaxel in previously treated HER2 + gastric or gastroesophageal junction adenocarcinoma—trial in progress . J Clin Oncol . 2021 ; 39 ( Suppl 3 ): TPS252 .

浏览量

Downloads

CSCD

文章被引用时，请邮件提醒。

Submit

工具集

关联资源

Ultrasound initiated tumor catalytic PANoptosis by mesoporous piezoelectric nanocatalysts

National age-specific mortality trends for cervical and breast cancers in urban-rural areas of China from 2009 to 2021: a population-based analysis

Gastroenteropancreatic neuroendocrine neoplasms: current development, challenges, and clinical perspectives

Reprogramming neural-tumor crosstalk: emerging therapeutic dimensions and targeting strategies

Immunotherapy for tuberculosis: current strategies and future directions