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Targeted Agents for HER2-Positive Breast Cancer: Optimal Use in Older Patients.

ABSTRACT: The HER2 gene is overexpressed in 15-20 % of all breast cancers. With the advent of HER2-directed therapies, HER2 overexpression is no longer considered an adverse prognostic factor. Despite significant improvements in clinical outcomes with the use of trastuzumab [herceptin (H)], women aged >65 years remain under-represented in most clinical trials. Cardiac safety in the elderly woman is a major concern because of pre-existing comorbidities. However, many studies suggest that elderly patients with HER2-positive disease derive the same benefit from trastuzumab as do their younger counterparts in both adjuvant and metastatic settings. Data are limited guiding safety and efficacy of other HER2 inhibitors such as pertuzumab and trastuzumab emtansine in elderly patients; however, in general, these drugs have a favorable toxicity profile.

SUBMITTER: Singh JC

PROVIDER: S-EPMC4991772 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature

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Targeted Agents for HER2-Positive Breast Cancer: Optimal Use in Older Patients.

Singh Jasmeet Chadha JC Lichtman Stuart M SM

Drugs & aging 20151201 12

The HER2 gene is overexpressed in 15-20 % of all breast cancers. With the advent of HER2-directed therapies, HER2 overexpression is no longer considered an adverse prognostic factor. Despite significant improvements in clinical outcomes with the use of trastuzumab [herceptin (H)], women aged >65 years remain under-represented in most clinical trials. Cardiac safety in the elderly woman is a major concern because of pre-existing comorbidities. However, many studies suggest that elderly patients w ...[more]

PMID: 26645293

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Project description:BackgroundTaxane, carboplatin and trastuzumab (TCH) is an effective neoadjuvant regimen for human epidermal growth factor receptor 2 (HER2)-positive breast cancer with high pathologic complete response (pCR) rate. The KATHERINE trial changes the outlook for high-risk HER2-positive breast cancer, which suggests that escalation treatment for patients with residual disease after neoadjuvant anti-HER2 therapy may improve survival. The major objective of this study was to investigate the fewest cycles of neoadjuvant TCH therapy needed to screen out non-pCR patients.MethodsThis retrospective study included patients with HER2-positive breast cancer who received either four or six cycles of TCH preoperatively at Fudan University Shanghai Cancer Center between 2008 and 2019. The pCR status was evaluated, and relevant factors associated with pCR were identified using univariate and multivariable analyses. The pathological results of core needle biopsy (CNB) in the breast tumor after two cycles of neoadjuvant chemotherapy were also collected. Kaplan-Meier curve was used to estimate the event-free survival (EFS).ResultsOf 758 eligible patients, 303 were included and analyzed in the four-cycle group and 455 in the six-cycle group. There was no significant difference between the two groups in terms of the pCR rate (46.5% [95% CI 40.9% - 52.2%] in the four-cycle group and 49.9% [95% CI 45.3% - 54.5%] in the six-cycle group, p = 0.365) or the four-year EFS (90.8% in four-cycle group and 93.8% in six-cycle group; p = 0.264). Multivariable analysis indicated that a negative hormone receptor status and the weekly paclitaxel were independent factors for predicting pCR. After adjusting for factors in the multivariable analysis, there was still no significant difference between four and six cycles of neoadjuvant TCH (OR = 1.252, 95% CI 0.904 - 1.733, p = 0.176). Furthermore, 17.9% patients with invasive carcinoma on CNB after two cycles of TCH ultimately achieved pCR in the breast after the completion of neoadjuvant treatment.ConclusionFour cycles of taxane/carboplatin-based neoadjuvant anti-HER2 therapy may be applied as an optimal treatment duration for screening high-risk HER2-positive breast cancer patients for escalation treatment. Further prospective study is warranted.

Project description:BackgroundClinical trials of human epidermal growth factor receptor 2 (HER2)-targeted agents added to standard treatment have been efficacious for HER2-positive (HER2+) advanced breast cancer. To our knowledge, no meta-analysis has evaluated HER2-targeted therapy including trastuzumab emtansine (T-DM1) and pertuzumab for HER2-positive breast caner and ranked the targeted treatments. We performed a network meta-analysis of both direct and indirect comparisons to evaluate the effect of adding HER2-targeted agents to standard treatment and examined side effects.MethodsWe performed a Bayesian-framework network meta-analysis of randomized controlled trials to compare 6 HER2-targeted treatment regimens and 1 naïve standard treatment (NST, without any-targeted drugs) in targeted treatment of HER2+ breast cancer in adults. These treatment regimens were T-DM1, LC (lapatinib), HC (trastuzumab), PEC (pertuzumab), LHC (lapatinib and trastuzumab), and PEHC (pertuzumab and trastuzumab). The main outcomes were overall survival and response rates. We also examined side effects of rash, LVEF (left ventricular ejection fraction), fatigue, and gastrointestinal disorders, and performed subgroup analysis for the different treatment regimens in metastatic or advanced breast cancer.ResultsWe identified 25 articles of 21 trials, with data for 11,276 participants. T-DM1 and PEHC were more efficient drug regimens with regard to overall survival as compared with LHC, LC, HC and PEC. The incidence of treatment-related rash occurs more frequently in the patients who received LC treatment regimen than PEHC and T-DM1 and HC. In subgroup analysis, T-DM1 was associated with increased overall survival as compared with LC and HC. PEHC was associated with increased overall response as compared with LC, HC, and NST.ConclusionsOverall, the regimen of T-DM1 as well as pertuzumab in combination with trastuzumab and docetaxel is efficacious with fewer side effects as compared with other regimens, especially for advanced HER2+ breast cancer.ImpactThis study suggests that both T-DM1 and PEHC therapy are potentially and equally useful treatments for HER2+ breast cancer.

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Targeted Agents for HER2-Positive Breast Cancer: Optimal Use in Older Patients.

Publications

Targeted Agents for HER2-Positive Breast Cancer: Optimal Use in Older Patients.

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