Long-term responders to trastuzumab monotherapy in first-line HER-2+ advanced breast cancer: characteristics and survival data

Abstract

Background The impact of HER2-targeted therapy alone followed by the addition of chemotherapy at disease progression (PD) versus upfront combination was investigated by the SAKK 22/99 trial. The aim of this exploratory analysis of the SAKK 22/99 trial was to characterize the specific subset of patients deriving long-term benefit from trastuzumab monotherapy alone and to identify potential predictive factors of long-term response. Methods This is an unplanned post-hoc analysis of patients randomized to Arm A (trastuzumab monotherapy). Patients were divided in two groups: patients with durable clinical benefit from trastuzumab monotherapy and short-term responders without durable clinical benefit from trastuzumab monotherapy Univariate and multivariate analyses of clinical characteristics correlating with response duration was performed. Results Eighty six patients were randomized in arm A, 24 patients (28%) were long-term responders and 62 (72%) were short-term responders with a 5y-overall survival (OS) of 54% (95% CI 31–72) and of 18% (95%CI 10–30), respectively. Absence of ER expression, absence of PgR expression and presence of visceral disease emerged as possible negative predictive factors for durable clinical benefit. Conclusion Durable clinical benefit can be achieved with trastuzumab monotherapy in a subgroup of HER2-positive patients with advanced disease and it is predictive for longer OS. Further investigations of predictive biomarkers are necessary to better characterize this subgroup of patients and develop further de-escalating strategies. Trial registration NCT00004935; first posted 27.01.2003, retrospectively registered.

Whole-exome sequencing of long-term, never relapse exceptional responders of trastuzumab-treated HER2+ metastatic breast cancer

“…Our investigation of genome-wide CNA burden offers the potential to gain insight into the underlying genetic landscape of long-term, never relapse exceptional response to trastuzumab. Recent analysis of the SAKK 22/99 trial identified that a subset of advanced HER2+ patients displayed long-term disease control with trastuzumab monotherapy; 14 however, this study was unable to identify any meaningful clinical predictive markers to characterise these patients. Therefore, our preliminary study supports our hypothesis that CNA burden may account for exceptional response to trastuzumab.…”

Trastuzumab therapy duration in HER2-positive de novo metastatic breast cancer: 1999–2018

“…Outcomes for the 37 CR patients remaining on therapy were not reported. Schmid et al found durable clinical benefit from trastuzumab monotherapy to be predictive of longer overall survival in HER2-positive advanced disease [ 20 ]. In a study of patients with at least 2 years first-line trastuzumab treatment, of those with a clinical complete response, four of twenty-five with T treatment interruption had progressive disease [ 21 ].…”

Aiming for the Cure in ERBB2-Positive Metastatic Breast Cancer—Should We Go “All In”?

“…When we analyze the curves of the pivotal trials mentioned by Tarantino et al, the considerable proportion of censored data and a small percentage of participants with long-term follow-up certainly impair conclusions . On the other hand, it is undeniable that roughly one-third of the long-term responders received chemotherapy plus trastuzumab, which suggests that for a substantial proportion of patients, trastuzumab is potentially enough, as also shown by other studies …”