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

BACKGROUND: The topic of trastuzumab therapy without chemotherapy in early breast cancer (EBC) has been repeatedly discussed at international consensus meetings, but is compromised by the lack of solid evidence from clinical studies. METHODS: An observational study database of patients with EBC receiving trastuzumab-containing (neo)adjuvant therapy was screened to identify those patients who did not receive cytostatic agents. RESULTS: Of 3935 patients, 232 (6%) were identified who received no chemotherapy, being characterized by older age, worse performance status, and/or less aggressive histology. Relapse-free survival in this cohort was 84% (95% confidence interval [CI] 78-89%) at 3 years and 80% (95% CI 74-87%) at 5 years. However, these rates were significantly worse than those in the group of patients who received chemotherapy (hazard ratio 1.49; 95% CI 1.06-2.09; P = 0.022). A similar pattern was observed for overall survival, with marginally non-significant inferiority in the group receiving no chemotherapy (hazard ratio 1.56; 95% CI 1.00-2.44; P = 0.052). Survival rates in patients receiving no chemotherapy were 93% (95% CI 88-97%) and 87% (95% CI 81-93%) at 3 and 5 years, respectively. These findings were confirmed by a propensity score analysis accounting for selection bias. CONCLUSIONS: Trastuzumab plus chemotherapy should remain the preferred option in all patients with HER2-positive EBC with an indication for adjuvant treatment. However, a limited proportion of patients will need an alternative treatment approach, either because of contraindications or the patient's preference. In these selected patients, trastuzumab monotherapy, eventually combined with endocrine agents, might be a reasonable option offering favorable long-term outcomes by addressing the high-risk profile associated with HER2-positive disease.

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.

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;22:131-138Implications 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.

Treosulfan in the Treatment of Advanced Ovarian Cancer - Results of a German Multicenter Non-interventional Study.

BACKGROUND: Data on routine systemic treatment of patients with ovarian cancer are currently available only to a limited degree. The alkylating agent treosulfan is approved in oral (p.o.) and intravenous (i.v.) form for the treatment of ovarian carcinoma. The present non-interventional study analyzed the clinical use of treosulfan in Germany, evaluating the mode of application, toxicity, and response and survival rate. PATIENTS AND METHODS: Two hundred and forty-eight ovarian cancer patients in 57 Centers, who received treosulfan mainly either i.v. (5,000-8,000 mg/m(2) d1, q21d or q28d) or p.o. (400-600 mg/m(2) d1-14 or 21, q28d) for at least one therapy cycle were evaluable and were included in the study. RESULTS: With a median age of 70 years (range=36-92 years), predominantly elderly patients received treosulfan treatment. Most participants presented serous histology (131, 52.8%) and advanced-stage FIGO III (122, 49%) or IV (55, 22%) disease. Median ECOG status was 1 (range=0-2), whereas cardiac co-morbidity was common (31%). Treosulfan was usually administered as second- (26%), third- (21%) or fourth-line (17%) therapy. Two hundred and one patients received i.v. and 47 p.o. TREATMENT: The most common reason for dose modifications was due to hematological toxicity (46%). The main reason for a therapy discontinuation was progressive disease (38.5%). Response was observed in 25.8% of participants, disease stabilization in 28.6 % and progress in 45.6%. The median progression-free and overall survival was 196 and 405 days, respectively. CONCLUSION: In predominantly elderly and heavily pre-treated patients with recurrent ovarian cancer, treosulfan featured a clinical relevant efficacy and well-manageable, mostly hematological, toxicity, which resulted in a positive therapeutic index.