Predicting for activity of second-line trastuzumab-based therapy in her2-positive advanced breast cancer

Abstract

BackgroundIn Her2-positive advanced breast cancer, the upfront use of trastuzumab is well established. Upon progression on first-line therapy, patients may be switched to lapatinib. Others however remain candidates for continued antibody treatment (treatment beyond progression). Here, we aimed to identify factors predicting for activity of second-line trastuzumab-based therapy.MethodsNinety-seven patients treated with > 1 line of trastuzumab-containing therapy were available for this analysis. Her2-status was determined by immunohistochemistry and re-analyzed by FISH if a score of 2+ was gained. Time to progression (TTP) on second-line therapy was defined as primary study endpoint. TTP and overall survival (OS) were estimated using the Kaplan-Meier product limit method. Multivariate analyses (Cox proportional hazards model, multinomial logistic regression) were applied in order to identify factors associated with TTP, response, OS, and incidence of brain metastases. p values < 0.05 were considered to indicate statistical significance.ResultsMedian TTP on second-line trastuzumab-based therapy was 7 months (95% CI 5.74-8.26), and 8 months (95% CI 6.25-9.74) on first-line, respectively (n.s.). In the multivariate models, none of the clinical or histopthological features could reliably predict for activity of second-line trastuzumab-based treatment. OS was 43 months suggesting improved survival in patients treated with trastuzumab in multiple-lines. A significant deterioration of cardiac function was observed in three patients; 40.2% developed brain metastases while on second-line trastuzumab or thereafter.ConclusionTrastuzumab beyond progression showed considerable activity. None of the variables investigated correlated with activity of second-line therapy. In order to predict for activity of second-line trastuzumab, it appears necessary to evaluate factors known to confer trastuzumab-resistance.

Trastuzumab Treatment beyond Progression in Advanced Breast Cancer: Patterns of Care in Six Swiss Breast Cancer Centers

“…Our results, which are similar to other retrospective studies, indicate that durable disease control can be achieved with repeated or prolonged exposure to trastuzumab. The median TTP of 6 months with second-line treatment in our study is consistent with reports in the literature [21,22] . The predominant chemotherapy partners in the second-line setting were vinorelbine and taxane, as in the first-line setting.…”

Impact of anti-HER2 therapy on overall survival in HER2-overexpressing breast cancer patients with brain metastases

“…An increase in the incidence of BM was observed in recent years, which is usually attributed to the introduction of trastuzumab-based therapy ( Bendell et al , 2003 ; Clayton et al , 2004 ; Shmueli et al , 2004 ; Burstein et al , 2005 ; Viani et al , 2007 ). Recently, it was reported that up to 40% of all HER2-positive metastatic breast cancer patients will be eventually diagnosed with BM ( Bartsch et al , 2009 ). Other studies, however, suggest that even in the absence of trastuzumab, women with HER2-positive metastatic breast cancer are at increased risk for BM as compared with women with HER2-negative disease ( Pestalozzi and Brignoli, 2000 ; Pestalozzi et al , 2006 ).…”

Impact of Her-2-Targeted Therapy on Overall Survival in Patients With Her-2 Positive Metastatic Breast Cancer

“…The mechanism of resistance to trastuzumab is still not fully understood. Consequently, the identification of clinical or histopathologic factors to define a population gaining benefit from trastuzumab continuation was unsuccessful so far . Only few possible immunologic characteristics such as immunoglobulin G Fragment C receptor polymorphisms were identified to predict for activity of trastuzumab in the induction of antibody‐dependent cytotoxicity .…”