Pyrotinib plus capecitabine for patients with human epidermal growth factor receptor 2-positive breast cancer and brain metastases (PERMEATE): a multicentre, single-arm, two-cohort, phase 2 trial

Yan, Min; Ouyang, Qi; Sun, Tao; Niu, Limin; Yang, Jin; Li, Li; Song, Yuhua; Hao, Chunfang; Chen, Zhan-Hong; Orlandi, Armando; Ishii, Naohiro; Takabe, Kazuaki; Franceschini, Gianluca; Ricci, Francesco; Verschraegen, Claire F.; Liu, Zhenzhen; Zhang, Mengwei; Lv, Haiyan; Liu, Liping; Yang, Xiaohong; Xiao, Huawu; Gao, Zhichao; Li, Xiaorui; Dong, Fangyuan; Chen, Xiuchun; Qiao, Jie; Zhang, Guifang

doi:10.1016/s1470-2045(21)00716-6

Cited by 86 publications

(98 citation statements)

References 27 publications

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“…It would provide important references for our clinical decision-making. (2) In recent years, relevant studies have reported that small-molecule tyrosine kinase inhibitors could improve the progression and prognosis of BM in HER2-positive BC patients ( 33 – 35 ). We expect that there could be some clinical trials about pre-emptive medical interventions in the future.…”

Section: Discussionmentioning

confidence: 99%

Risk Factors of Brain Metastasis and Prognosis in HER2-Positive Breast Cancer: A Single-Institution Retrospective Analysis from China

et al. 2022

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BackgroundBrain metastasis (BM) frequently occurs in HER2-positive breast cancer (BC) patients, but the risk factors of BM in this type of patients are still unknown. Our study aims to assess the risk factors of BM and prognostic analysis in HER2-positive BC patients.MethodsUnivariate analysis used t-test, chi-square test, and Fisher’s exact test to find out the risk factors for BM, and multivariable analysis was done with stepwise logistic regression analysis. Prognostic data analysis was estimated by the Kaplan–Meier method.ResultsA total of 228 HER2-positive BC patients were included, of whom 214 patients were postoperative metastatic patients and 14 patients were de novo stage IV patients. Through comparing the stratified variables between 51 postoperative metastatic patients with BM and 163 postoperative metastatic patients without BM, the multivariate analysis showed that age ≤40 years (OR 2.321, 95% CI: 1.089 to 4.948) and first metastatic site with lung metastasis (OR 2.168, 95% CI: 1.099 to 4.274) were independent risk factors for BM in HER2-positive BC patients. Prognostic data of all 65 HER2-positive BC patients with BM showed that the time from the diagnosis of BC to the development of breast cancer brain metastasis (BCBM) was 36.3 months (95% CI: 30.0 to 42.1 months). The time from the diagnosis of first recurrence and metastasis stage to the diagnosis of BCBM was 11.35 months (95% CI: 7.1 to 18.4 months). The time from the diagnosis of BCBM to the time of follow-up was 24.1 months (95% CI: 13.9 to 37.5 months). Up until the time of follow-up data, a total of 38 patients had died, and the time from the diagnosis of BM of these 38 patients to death was 11.0 months (95% CI: 9.0 to 20.4 months).ConclusionThe prognosis of HER2-positive BC patients with BM was poor due to the lack of effective treatments for BM. Age ≤40 years and first metastatic site with lung metastasis were the independent risk factors for BM in HER2-positive BC patients. Future research about pre-emptive medical interventions may help to improve the prognosis of HER2-positive BC patients with high risk to develop BM.

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Section: Discussionmentioning

confidence: 99%

Risk Factors of Brain Metastasis and Prognosis in HER2-Positive Breast Cancer: A Single-Institution Retrospective Analysis from China

et al. 2022

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“…49,50 Pyrotinib is a novel HER2-targeted therapy approved in China for patients with pretreated HER2-positive MBC. In the phase II PERME-ATE study, the CNS objective response rate with pyrotinib/ capecitabine was 74.6% in CNS radiation-naive patients and 42.1% in patients with progressive disease after CNS radiation, supporting 51 CNS activity of the regimen. Last, the randomized, placebo-controlled HER2CLIMB trial evaluated the combination of tucatinib/trastuzumab/capecitabine versus placebo/trastuzumab/capecitabine in patients with HER2-positive MBC with or without brain metastases.…”

Section: Treatment Of Patients With Her2-positive Brain Metastasesmentioning

confidence: 89%

Systemic Therapy for HER2-Positive Metastatic Breast Cancer: Moving Into a New Era

Gión

Trapani

Cortés

et al. 2022

American Society of Clinical Oncology Educational Book

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Patients with HER2-positive breast cancer account for approximately 15% to 20% of all breast cancers and represent one of the most aggressive breast cancer subtypes. Survival rates of patients with metastatic disease have improved dramatically and progressively. Many new agents have been developed, and long-term follow-up from trials of anti-HER2 agents has shown long-term responses. The availability of novel, highly active anti-HER2 treatments, together with the ongoing development of promising diagnostic tools, will offer the unprecedented opportunity to raise cure rates. Our ultimate goal is to tailor treatment intensity to disease and patient characteristics, hopefully increasing the fraction of cured patients while minimizing the risk for overtreatment. If conducted rationally and carefully, this plan has the potential to break a decades-long paradigm, leading to a new, precise era of treatment of HER2-positive breast cancer.

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“… 31 This irreversible dual pan-ErbB receptor TKI was assessed in the phase II PERMEATE trial, whose results have been recently published on The Lancet Oncology, reporting an ORR of 74.6% in the central nervous system. 32 However, patients experiencing disease progression following stereotactic radiation therapy or whole-brain radiotherapy presented an overall lower ORR (42.1%). In addition, median PFS was significantly longer in the radiation therapy – naïve cohort (12.1 months) compared with the radiotherapy cohort (5.6 months).…”

Section: Second-line Treatmentmentioning

confidence: 96%

“…In terms of treatment-related adverse events, the most frequently observed grade 3 toxicity was diarrhea (23.1%), followed by hematological toxicities, including decreased neutrophil cell count (12.8%), decreased white blood cell count (12.8%), and anaemia (9%). 32 …”

Section: Second-line Treatmentmentioning

confidence: 99%

Systemic Treatments for Metastatic Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer: Old Certainties and New Frontiers

et al. 2022

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Epidermal growth factor receptor 2 (EGFR2, also known as HER2) overexpression and/or amplification confers a more aggressive clinical behavior but also represents a therapeutic opportunity for targeted therapies in breast cancer (BC). Over the last 2 decades, the prognosis of HER2-positive metastatic BC patients has improved due to the introduction of anti-HER2 agents including trastuzumab and novel, emerging drugs and combinations such as trastuzumab deruxtecan and tucatinib – trastuzumab - capecitabine. Herein, we provide a critical overview of current clinical recommendations and emerging treatment options for metastatic HER2-positive BC, especially focusing on recently presented and published clinical trials in this setting.

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Pyrotinib plus capecitabine for patients with human epidermal growth factor receptor 2-positive breast cancer and brain metastases (PERMEATE): a multicentre, single-arm, two-cohort, phase 2 trial

Cited by 86 publications

References 27 publications

Risk Factors of Brain Metastasis and Prognosis in HER2-Positive Breast Cancer: A Single-Institution Retrospective Analysis from China

Risk Factors of Brain Metastasis and Prognosis in HER2-Positive Breast Cancer: A Single-Institution Retrospective Analysis from China

Systemic Therapy for HER2-Positive Metastatic Breast Cancer: Moving Into a New Era

Systemic Treatments for Metastatic Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer: Old Certainties and New Frontiers

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