Clinical outcome of patients with brain metastases from HER2-positive breast cancer treated with lapatinib and capecitabine

Metro, Giulio; Foglietta, Jennifer; Russillo, Michelangelo; Stocchi, Lucia; Vidiri, Antonello; Giannarelli, Diana; Crinò, Lucio; Papaldo, Paola; Mottolese, Marcella; Cognetti, Francesco; Fabi, Alessandra; Gori, Stefania

doi:10.1093/annonc/mdq434

Cited by 149 publications

(85 citation statements)

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“…In our study, 23 patients were HER2-positive, and 11 (48%) of them had received lapatinib treatment before enrolling in this trial. The clinical efficacy of the BEEP regimen for the HER2-positive subgroup in our study was higher than that observed in clinical trials in which lapatinib and capecitabine were administered to patients who were previously treated with WBRT (7)(8)(9). In a recent study that was restricted to HER2-positive patients who had not been previously treated with WBRT (24), the clinical efficacy, according to the objective CNS response rate (65.9% according to RECIST) and the median TTP (5.5 months), was similar to that observed in our study.…”

Section: Discussioncontrasting

confidence: 71%

“…We aimed for a 30% CNS-ORR of the BEEP regimen based on previous studies of brain metastasis of breast cancer patients (7)(8)(9), as well as the traditional view that the efficacy of salvage chemotherapy is expected to be lower in later lines of chemotherapy, which is widely observed in patients who have undergone WBRT. The results demonstrated that the BEEP regimen had a CNS-ORR of 77%, which was considerably higher than expected.…”

Section: Discussionmentioning

confidence: 99%

“…Prospective clinical studies that have focused on treating breast cancer with progressive brain metastases after WBRT are limited to HER2-positive subtype. A treatment combining capecitabine with lapatinib, a small-molecule anti-HER2-targeted agent, resulted in a response rate of 18% to 38% and a time-to-progression (TTP), or progression-free survival (PFS), of 2.8 to 5.1 months in HER2-positive patients with brain metastases who had been predominantly (86%-100%) pretreated with WBRT (7)(8)(9).…”

Section: Introductionmentioning

confidence: 99%

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Bevacizumab Preconditioning Followed by Etoposide and Cisplatin Is Highly Effective in Treating Brain Metastases of Breast Cancer Progressing from Whole-Brain Radiotherapy

Chen

Lin

et al. 2015

Clinical Cancer Research

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Purpose: We hypothesized that a window period between bevacizumab and cytotoxic agents may enhance drug delivery into tumor tissue through bevacizumab-induced vascular normalization in patients with brain metastases of breast cancer (BMBC).Experimental Design: A single-arm phase II study was conducted in which BMBC patients refractory to whole-brain radiotherapy (WBRT) were enrolled. In a 21-day cycle, patients received bevacizumab (15 mg/kg) on day 1, which, with a 1-day window period, was followed by etoposide (70 mg/m 2 /day; days 2-4) and cisplatin (70 mg/m 2 ; day 2; BEEP regimen). The BEEP regimen was administered for a maximum of 6 cycles. The primary endpoint was the central nervous system (CNS)-objective response rate according to volumetric response criteria.Results: A total of 35 patients were enrolled between January 2011 and January 2013. The median age was 54.3 years (range, 33-75); 19 patients (54.3%) had an Eastern Cooperative Oncology Group performance status of 2 or 3. Twenty-seven patients [77.1%; 95% confidence interval (CI), 59.9-89.6] achieved a CNS-objective response, including 13 patients (37.1%) with a !80% volumetric reduction of CNS lesions. With a median follow-up of 16.1 months, the median CNS progression-free survival and overall survival times were 7.3 months (95% CI, 6.5-8.1) and 10.5 months (95% CI, 7.8-13.2), respectively. Common grade 3 or 4 toxicities included neutropenia (30.8%) and infection (21.3%).Conclusions: By administering bevacizumab 1 day before etoposide and cisplatin, the BEEP regimen appeared highly effective in BMBC refractory to WBRT. Further study of vascular normalization window concept is warranted.

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Section: Discussioncontrasting

confidence: 71%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Bevacizumab Preconditioning Followed by Etoposide and Cisplatin Is Highly Effective in Treating Brain Metastases of Breast Cancer Progressing from Whole-Brain Radiotherapy

Chen

Lin

et al. 2015

Clinical Cancer Research

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“…2,3 In addition, it showed interesting activity in patients with brain metastasis. [4][5][6][7] Skin rash, diarrhea, and hepatic toxicities are adverse events (AEs) that have been linked with not only lapatinib, [8][9][10][11] but also other EGFR TKIs.…”

Section: Introductionmentioning

confidence: 99%

Pattern of Rash, Diarrhea, and Hepatic Toxicities Secondary to Lapatinib and Their Association With Age and Response to Neoadjuvant Therapy: Analysis From the NeoALTTO Trial

Azim

Agbor-Tarh

Bradbury

et al. 2013

JCO

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Purpose We investigated the pattern of rash, diarrhea, and hepatic adverse events (AEs) secondary to lapatinib and their association with age and pathologic complete response (pCR) in the Neoadjuvant Lapatinib and/or Trastuzumab Treatment Optimisation (NeoALLTO) phase III trial. Patients and Methods Patients with HER2-positive early breast cancer were randomly assigned to receive lapatinib (Arm A), trastuzumab (Arm B), or their combination (Arm C) for 6 weeks followed by the addition of paclitaxel for 12 weeks before surgery. We investigated the frequency and time to developing each AE according to age (≤ 50 v > 50 years) and their association with pCR in a logistic regression model adjusted for age, hormone receptors, tumor size, nodal status, planned breast surgery, completion of lapatinib administration, and treatment arm. Results Only patients randomly assigned to arms A and C were eligible (n = 306). Younger patients (≤ 50 years) experienced significantly more rash compared with older patients (74.4% v 47.9%; P < .0001). Diarrhea and hepatic AEs were observed in 78.8% and 41.2% of patients, respectively, with no differences in rate or severity or time of onset according to age. Early rash (ie, before starting paclitaxel) was independently associated with a higher chance of pCR, mainly in patients older than 50 years (odds ratio [OR] = 3.76; 95% CI, 1.69 to 8.34) but not in those ≤ 50 years (OR = 0.92; 95% CI, 0.45 to 1.88; P for interaction = .01). No significant association was observed between pCR and diarrhea or hepatic AEs. Conclusion Our results indicate that the frequency and clinical relevance of lapatinib-related rash is largely dependent on patient age.

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“…При оценке частоты ответа метастазов в ГМ у ранее леченных больных лапатиниб в монотерапии показал эффективность в пределах от 2,6 до 6,0 % [31,32]. При добавлении капецитабина частота ответа воз-растала до 20-33 % [33][34][35][36]. Самая высокая эффектив-ность наблюдалась у ранее не леченных больных: ча-стота объективного ответа при сочетании лапатиниба и капецитабина достигала 65,9 % с медианой времени до прогрессирования 5,5 мес и 1-годичной выжива-емостью > 70 % [37].…”

Section: опухоли женской репродуктивной системы Tumors Of Female Reprunclassified

Role of targeted therapy in the treatment of HER-2-positive breast cancer brain metastases

Дашян¹,

Семиглазов²,

Krivorotko³

et al. 2016

Tumors of female reproductive system

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46М а м м о л о г и я / M a m m o l o g y 1 ' 2 0 1 6 Том 12 / Vol. 12 ОПУХОЛИ ЖЕНСКОЙ РЕПРОДУКТИВНОЙ СИСТЕМЫ TUMORS OF FEMALE REPRODUCTIVE SYSTEM Лечение После рака легких 2-й наиболее частой причиной метастазов в головной мозг (ГМ) является рак мо-лочной железы (РМЖ), метастазирование при кото-ром наблюдается в 10-16 % случаев [1]. Еще у 10 % больных происходит бессимптомное метастазирова-ние, что подтверждается данными аутопсии [2]. В по-следние годы отмечается более частое выявление метастазов в ГМ, что, вероятно, связано с более дли-тельной выживаемостью больных, получающих со-временные эффективные методы лечения, а также с применением более чувствительных методов визу-ализации.Развитие метастазов в ГМ представляет собой сложный процесс, предполагающий инвазию клеток РМЖ в окружающие ткани и сосуды, циркуляцию

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Clinical outcome of patients with brain metastases from HER2-positive breast cancer treated with lapatinib and capecitabine

Abstract: LC is active for BMs from HER2+ BC in patients not pretreated with either lapatinib or capecitabine. The introduction of LC after the development of BMs may further improve survival compared with trastuzumab-based therapies only beyond brain progression.

Cited by 149 publications

References 26 publications

Bevacizumab Preconditioning Followed by Etoposide and Cisplatin Is Highly Effective in Treating Brain Metastases of Breast Cancer Progressing from Whole-Brain Radiotherapy

Bevacizumab Preconditioning Followed by Etoposide and Cisplatin Is Highly Effective in Treating Brain Metastases of Breast Cancer Progressing from Whole-Brain Radiotherapy

Pattern of Rash, Diarrhea, and Hepatic Toxicities Secondary to Lapatinib and Their Association With Age and Response to Neoadjuvant Therapy: Analysis From the NeoALTTO Trial

Role of targeted therapy in the treatment of HER-2-positive breast cancer brain metastases

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