Pyrotinib combining with radiotherapy on breast cancer with brain metastasis

Abstract

With the extensive application of anti-human epidermal growth factor receptor-2 (HER2) targeted therapy, the prognosis of HER2-positive breast cancer brain metastasis (BCBM) has been improved greatly. Due to the lack of prospective randomized controlled studies; however, the treatment of active brain metastasis (BM) remains a difficulty in clinic. Based upon the retrospective studies, an effective approach of radiotherapy combined with pyrotinib in HER2-positive BCBM treatment was investigated in present research. In all, 29 patients who had active BM in HER2-positive breast cancer (BC) and underwent whole-brain radiotherapy (WBRT) combined with pyrotinib from January 2019 to May 2021 were enrolled. The progression-free survival (PFS), overall survival (OS), clinical benefit rate (CBR), objective response rate (ORR), and drug-related adverse events (AEs) were analyzed among patients undergoing WBRT combined with concurrent or sequence pyrotinib + capecitabine. After the systematic treatments using WBRT combined with pyrotinib + capecitabine, the mPFS and mOS of BM patients were 6.5 months and 15.5 months, respectively. PFS (7.2 vs 6.2 months, p = 0.038) and OS (19.0 vs 14.0 months, p = 0.014) were longer after sequence treatments than those after concurrent treatment. The central nervous system (CNS) ORR of sequence treatment was superior to that of concurrent treatment (80.4% vs 58.6%, p < 0.05). Vomiting (17.2%) and diarrhea (10.3%) were the most common adverse reactions ⩾ grade 3. WBRT combined with pyrotinib is safe and effective for the treatments of active BM in HER2-positive BC. WBRT combined with sequence pyrotinib + capecitabine is more effective and less toxic than concurrent treatment. Therefore, sequence treatment is potentially a preferred regimen for patients with active BM in HER2-positive BC. The size and number of BM lesions, presence or absence of hepatic metastasis, and combination mode of radiotherapy and targeted therapy are independent risk factors for active BM prognosis.

Efficacy and Safety of Radiotherapy Combined with Pyrotinib in the Treatment of HER2-Positive Breast Cancer with Brain Metastases

“…The results showed that T stage, ECOG score, lung, liver, bone metastases, number of BM, and radiotherapy mode were possible predictors of OS in patients. This is in agreement with Hackshaw 46 Ma et al 31 After multifactorial Cox regression analysis, we found that ECOG score, number of BM, and radiotherapy mode were independent prognostic factors for OS in patients. In a study from the SEER database (n = 206913), the incidence of BM was higher in patients with multiple extracranial metastases (bone, liver, and lung) than in patients with bone metastases alone (28.0% vs 8.6%), suggesting that visceral metastases are a risk factor for BM.…”

“…48 Brain MRI screening is only recommended when a patient has symptoms of suspected intracranial metastases, and the chances of early treatment of BM will be greater if closer brain monitoring can be performed when the patient has high-risk factors like visceral metastases. 27 Showing no difference with earlier issued data, 31,36 The security analysis of this research showed that the most usual untoward reaction was diarrhea. No critical untoward reaction was observed in either group, suggesting that the overall safety tolerability of pyrotinib for BM was acceptable, the safety of radiotherapy combined with pyrotinib was manageable, and the addition of radiotherapy did not significantly increase side effects in patients.…”

“…Recently published data suggest that the addition of most types of targeted therapies is safe and does not increase radiotherapy toxicity. [29][30][31] All of the above studies have shown the role of drugs and radiotherapy in HER2-positive BCBM, however, there are few data on the combination of radiotherapy and pyrotinib in the treatment of HER2-positive BCBM in the real world, and no study has shown which radiotherapy fractionation mode can achieve the best efficacy. The aim of this paper is to investigate the efficacy and safety of radiotherapy combined with pyrotinib and different modes of radiotherapy fractionation in patients with HER2-positive BCBM, in order to determine the best treatment mode for these patients.…”