A Clinical Study of Darcilil Combined With AI Combined With Pyrrotinib in the Treatment of TPBC

Summary

Elderly patients with advanced triple-positive breast cancer have the characteristics of low physical status and poor treatment tolerance. Therefore, such patients are often unable to tolerate more toxic chemotherapy regimen, and it is particularly important to choose a highly effective and low-toxic treatment regimen. However, few studies have paid attention to the treatment of such patients in the past. Pyrrotinib is a small molecule, irreversible, panerbb receptor tyrosine kinase inhibitor, which was independently developed by our country and has shown excellent efficacy in second-line anti-HER2 treatment of breast cancer, and has become the second-line standard treatment choice for advanced HER2-positive breast cancer. In addition, PHILA study results showed that the mPFS of pyrrotinib group reached 24 months. Compared with the control group, the duration of 10 months was significantly extended, indicating the significant efficacy of pyrrotinib in the first-line treatment of advanced HER2-positive breast cancer. Darsili is a CDK4/6 inhibitor independently developed in China, which has been reconstructed and optimized in molecular structure, and has become a new CDK4/6 inhibitor with more powerful modification by introducing piperidine structure through replacement of classical electronic and other panbody. The results of DAWNA-2 study indicated that the mPFS of Dalsily combined AI group reached 30.6 months, which was significantly longer than 18.2 months of the control group, and was the longest in similar studies. MUKDEN01 study, for the first time, tried the efficacy of pyrrotinib + letrozole + Dalsily regimen in the new adjuvant therapy of TPBC patients, and the results showed that ORR reached 87.4%, CR rate was 30.4%, and pCR rate was 35.4%. Therefore, to further confirm the efficacy and safety of this protocol in elderly patients with advanced triple positive breast cancer, we intend to conduct this study. This is a prospective, single-arm, single-center clinical trial in which participants were treated with darcilide +AI (letrozole/anastrozole/exemestane) + pyrrotinib until disease progression, toxicity became intolerable, informed consent was withdrawn, or investigator judgment required discontinuation. The successful development of this study provides a new direction for the first-line treatment of elderly advanced triple-positive breast cancer.

Timeline

Start

2024-02-01

Primary completion

2025-12-01

Completion

2026-12-01

Publications

• Results Zhang P, Zhang Q, Tong Z, Sun T, Li W, Ouyang Q, Hu X, Cheng Y, Yan M, Pan Y, Teng Y, Yan X, Wang Y, Xie W, Zeng X, Wang X, Hu C, Geng C, Zhang H, Li W, Wu X, Zhong J, Xu J, Shi Y, Wei W, Bayaxi N, Zhu X, Xu B. Dalpiciclib plus letrozole or anastrozole versus placebo plus letrozole or anastrozole as first-line treatment in patients with hormone receptor-positive, HER2-negative advanced breast cancer (DAWNA-2): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2023 Jun;24(6):646-657. doi: 10.1016/S1470-2045(23)00172-9. Epub 2023 May 11.
• Results Marty M, Cognetti F, Maraninchi D, Snyder R, Mauriac L, Tubiana-Hulin M, Chan S, Grimes D, Anton A, Lluch A, Kennedy J, O'Byrne K, Conte P, Green M, Ward C, Mayne K, Extra JM. Randomized phase II trial of the efficacy and safety of trastuzumab combined with docetaxel in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer administered as first-line treatment: the M77001 study group. J Clin Oncol. 2005 Jul 1;23(19):4265-74. doi: 10.1200/JCO.2005.04.173. Epub 2005 May 23.
• Results Wu J, Jiang Z, Liu Z, Yang B, Yang H, Tang J, Wang K, Liu Y, Wang H, Fu P, Zhang S, Liu Q, Wang S, Huang J, Wang C, Wang S, Wang Y, Zhen L, Zhu X, Wu F, Lin X, Zou J. Neoadjuvant pyrotinib, trastuzumab, and docetaxel for HER2-positive breast cancer (PHEDRA): a double-blind, randomized phase 3 trial. BMC Med. 2022 Dec 27;20(1):498. doi: 10.1186/s12916-022-02708-3.
• Results Kaufman B, Mackey JR, Clemens MR, Bapsy PP, Vaid A, Wardley A, Tjulandin S, Jahn M, Lehle M, Feyereislova A, Revil C, Jones A. Trastuzumab plus anastrozole versus anastrozole alone for the treatment of postmenopausal women with human epidermal growth factor receptor 2-positive, hormone receptor-positive metastatic breast cancer: results from the randomized phase III TAnDEM study. J Clin Oncol. 2009 Nov 20;27(33):5529-37. doi: 10.1200/JCO.2008.20.6847. Epub 2009 Sep 28.
• Results Huober J, Fasching PA, Barsoum M, Petruzelka L, Wallwiener D, Thomssen C, Reimer T, Paepke S, Azim HA, Ragosch V, Kubista E, Baumgartner AK, Beckmann MW, May C, Nimmrich I, Harbeck N. Higher efficacy of letrozole in combination with trastuzumab compared to letrozole monotherapy as first-line treatment in patients with HER2-positive, hormone-receptor-positive metastatic breast cancer - results of the eLEcTRA trial. Breast. 2012 Feb;21(1):27-33. doi: 10.1016/j.breast.2011.07.006. Epub 2011 Sep 8.
• Results Niu N, Qiu F, Xu Q, He G, Gu X, Guo W, Zhang D, Li Z, Zhao Y, Li Y, Li K, Zhang H, Zhang P, Huang Y, Zhang G, Han H, Cai Z, Li P, Xu H, Chen G, Xue J, Jiang X, Jahromi AH, Li J, Zhao Y, de Faria Castro Fleury E, Huo S, Li H, Jerusalem G, Tripodi D, Liu T, Zheng X, Liu C. A multicentre single arm phase 2 trial of neoadjuvant pyrotinib and letrozole plus dalpiciclib for triple-positive breast cancer. Nat Commun. 2022 Nov 17;13(1):7043. doi: 10.1038/s41467-022-34838-w.
• Results Zhang J, Meng Y, Wang B, Wang L, Cao J, Tao Z, Li T, Yao W, Hu X. Dalpiciclib Combined With Pyrotinib and Letrozole in Women With HER2-Positive, Hormone Receptor-Positive Metastatic Breast Cancer (LORDSHIPS): A Phase Ib Study. Front Oncol. 2022 Mar 7;12:775081. doi: 10.3389/fonc.2022.775081. eCollection 2022.
• Results Spring LM, Gupta A, Reynolds KL, Gadd MA, Ellisen LW, Isakoff SJ, Moy B, Bardia A. Neoadjuvant Endocrine Therapy for Estrogen Receptor-Positive Breast Cancer: A Systematic Review and Meta-analysis. JAMA Oncol. 2016 Nov 1;2(11):1477-1486. doi: 10.1001/jamaoncol.2016.1897.

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