Trastuzumab in Human Epidermal Growth Factor Receptor 2-Positive Early Breast Cancer: Results of a Prospective, Noninterventional Study on Routine Treatment Between 2006 and 2012 in Germany

Abstract

Purpose. Trastuzumab is part of the standard treatment in patients with human epidermal growth factor receptor 2-positive early breast cancer in addition to (neo)adjuvant chemotherapy. This German prospective noninterventional study, which included major patient cohorts underrepresented in the pivotal randomized studies, examined the generalizability of the results of those studies. Patients and Methods. Between 2006 and 2012, 4,027 patients were enrolled and treated with trastuzumab; they were unselected regarding age or concomitant/sequential adjuvant chemotherapy. Long-term outcome data were obtained in yearly intervals. All analyses were descriptive in nature. Results. Among 3,940 evaluable patients, 26% were elderly (older than 65 years of age). More than half of the population had pN0 tumor stage. Ninety-four percent received chemotherapy: 78% as adjuvant treatment and 14% as neoadjuvant treatment, 2% both. Anthracyclines were administered in 87% and taxanes in 66%. Trastuzumab was stopped prematurely in 9% (because of cardiotoxicity in 3.5%). Recurrence-free survival was 90.0% (95% confidence interval [CI], 88.9%-91.1%) and 82.8% (95% CI, 81.2%-84.4%) after 3 and 5 years, respectively. The corresponding figures for overall survival were 96.8% (95% CI, 96.1%-97.6%) and 90.0% (95% CI, 88.6%-91.4%). Pathological primary tumor size, lymph node involvement, and hormone receptor status had the greatest independent effect on recurrence risk. Cardiac function toxicity of National Cancer Institute common toxicity criteria grade 2 and 3 was observed in 2.5% and less than 1% of patients, respectively. Conclusion. The maturing follow-up data seem to confirm the beneficial results of trastuzumab treatment for early breast cancer from the randomized studies. Moreover, these findings support use of trastuzumab-based therapy in patients groups less commonly included in the phase III trials (e.g., elderly patients and those with stage I disease). The Oncologist 2017;22:131-138 Implications for Practice: On the basis of the results of large pivotal phase III studies, the inclusion of trastuzumab in adjuvant treatment regimens for human epidermal growth factor receptor 2-positive breast cancer is standard of care. However, in these trials, elderly patients, those with comorbidities, and/or those with contraindications or refusal of cytotoxic chemotherapy are typically underrepresented. This study provides data on observed treatment options, outcomes, and risks in a wider, unselected patient population (including more than 1,000 patients with stage I disease), treated routinely in several institutions of varying size and location across Germany.

Trastuzumab without chemotherapy in the adjuvant treatment of breast cancer: subgroup results from a large observational study

“…However, the general recommendations for heart function assessment were not followed in a considerable number of patients. The rate of patients having echocardiography was only around 60% per three-month time interval [ 14 ]. Other presumed adverse drug reactions of severity grade 3/4 were rare in the monotherapy group: two cases of cardiac arrhythmia, two cases of dyspnea or other lung toxicity, and one patient with elevated liver enzymes.…”

“…Details of the organizational and legal framework of this non-interventional study (Roche ML20315), the selection criteria for inclusion in the observation procedure, and the scope of the documentation have been described previously [ 14 ]. In general, patients were treated and their disease course was assessed according to routine practice at the treating institution.…”

“…This observational study [ 14 ] was started immediately after marketing authorization was received for Herceptin™ (trastuzumab) treatment in EBC. Its purpose was to obtain real-world evidence on routine usage of trastuzumab in Germany.…”

Long-Term Safety and Real-World Effectiveness of Trastuzumab in Breast Cancer

“…Some of the included patient subgroups were not commonly presented in phase III trials (e.g., elderly patients and patients with stage I disease). The overall survival rates at 3 and 5 years seem to confirm the advantage conferred by trastuzumab use in eBC [26].…”

Adding pertuzumab to adjuvant therapy for high-risk HER2-positive early breast cancer in APHINITY: a GRADE analysis

“…In the trastuzumab arms of the BCIRG-006 (Breast Cancer International Research Group 006) trial, 25% of patients eventually developed a 10-year DFS event (30% in case of LN+ disease) [5]. Moreover, it has been observed that pathological primary tumor size, LN involvement, and hormone receptor status have the greatest independent effect on recurrence risk [6].…”