Trastuzumab in advanced breast cancer--a decade of experience in Germany.

BACKGROUND: Trastuzumab was registered in 2000 for the treatment of metastatic breast cancer, both as monotherapy and combination therapy with paclitaxel. In this prospective, non-interventional observation study, the 10-year experience with trastuzumab in the routine management of HER2-positive breast cancer was reviewed. METHODS: Between 2000 and 2010, 1843 evaluable patients with advanced HER2-positive breast cancer were recruited in 223 institutions across Germany. Patients were prospectively monitored for about one year. Additional information on long-term outcomes, progression-free survival (PFS), and overall survival (OS) were retrieved at several follow-up points. There were no restrictions with respect to diagnostic or therapeutic procedures. Patients were stratified into three cohorts depending on the treatment regimen, i.e. trastuzumab monotherapy (n=228, 12%), trastuzumab combined with chemotherapy (n=1346, 73%), or trastuzumab combined with endocrine therapy (n=269, 15%). RESULTS: Median age was 59.5 years with a proportion of 28% being older than 65 years. Over a maximum follow-up period of more than 10 years, 1538 PFS events were documented in 83% of patients, resulting in an estimated median PFS of 11.8 months. Median OS, based on recorded death in 64% of patients, amounted to 34.4 months, with 48% (95% confidence intervals 45-50%) still alive after three years. The subgroup selected for a treatment combination with endocrine drugs only had distinctly longer PFS and OS than the other two groups, achieving medians of 23.3 months and 56.3 months, respectively. Median PFS and OS in elderly patients over 65 years of age was 11.4 months and 28.3 months, respectively. Adverse reactions, including cardiac toxicity, of severity grade 3 or 4 were rare. CONCLUSIONS: The superior outcome of treatment strategies including trastuzumab in HER2 overexpressing breast cancer, proven in pivotal studies, was confirmed in the management of advanced breast cancer in Germany in the routine setting. Our data suggest a comparable clinical benefit of treatment with trastuzumab in elderly patients (>65 years), who are typically under-represented in randomized clinical studies.

A new concept for the differential diagnosis and therapy of anaemia in cancer patients.

PURPOSE: This study aimed to prove the usefulness of the diagnostic plot, using the haemoglobin content of reticulocytes as a measure of functional iron deficiency (FID) and the ferritin index as a measure of iron availability, to customise anaemia treatment in cancer patients. METHODS: Based on results of this plot, cancer patients fulfilling practice guideline criteria to receive erythropoiesis-stimulating agents (ESAs) were allocated to treatment with ESAs alone, iron alone or the combination of both. Primary endpoint was the percentage of patients identified to require iron in addition or as an alternative to ESA therapy. RESULTS: Out of 303 patients screened, 286 were allocated to treatment: 204 patients were normochromic and iron replete and treated with ESAs alone, 22 had both FID and anaemia of chronic disease and were treated with ESAs and parenteral iron, and 60 were iron-depleted and treated with iron only. After 8 weeks, a haemoglobin increase >1 g/dL from baseline was shown by 56% of patients treated with ESAs alone, by 100% of patients receiving the combination, by 50% of normochromic and by 73% of hypochromic iron-depleted patients receiving iron only. Acute phase reaction did not diminish the response rate to ESAs. CONCLUSIONS: The diagnostic plot was superior to transferrin saturation and ferritin in predicting iron availability in hypochromic patients treated with ESAs and proved useful to select treatment for anaemia in cancer patients.

Trastuzumab in the treatment of elderly patients with early breast cancer: Results from an observational study in Germany.

BACKGROUND: In elderly patients with HER2-positive breast cancer, few data on efficacy and toxicity of adjuvant trastuzumab treatment exists since older patients were in general excluded from large randomized studies. This prospective observational study aimed to confirm the beneficial findings from pivotal trials in age cohorts ≥65 years. MATERIALS AND METHODS: There were no restrictions for recruitment with respect to age or concomitant/sequential adjuvant medication. Long-term relapse/survival status of the patients was assessed once a year. RESULTS: Among the 3940 evaluable patients enrolled between 2006 and 2012 at 339 institutions, 507 were aged between 65 and 69 years, with another 507 patients ≥70 years. Elderly patients suffered from significantly more advanced primary tumors. Preceding or concomitant chemotherapy showed decreasing aggressiveness with patient's age. Trastuzumab treatment was stopped prematurely in only 11% of the elderly, but more often than in younger patients (p=0.0008). With 453 events hitherto reported, elderly patients did not exhibit an inferior relapse-free survival when adjusted for other relevant prognostic factors (hazard ratio: 1.01 per year; p=0.24). Three-year overall survival was significantly lower in the population older than 64 years than in younger patients (94.2% vs. 96.8%, p=0.0011). CONCLUSIONS: To our knowledge, our population of elderly patients treated with adjuvant trastuzumab is the largest analyzed so far. The beneficial long-term results were comparable to those in the younger cohorts. Although the risk of cardiotoxicity increased significantly with age, it also remained manageable in older patients. Thus, chronological age alone should not preclude HER2 antibody treatment.