Supplementary Material for: AGO Recommendations for Diagnosis and Treatment of Patients with Early and Metastatic Breast Cancer: Update 2012

Medicin

Supplementary Material for: Sorafenib in the Treatment of Early Breast Cancer: Results of the Neoadjuvant Phase II Study - SOFIA*

<b><i>Background: </i></b>Sorafenib was tested for neoadjuvant treatment with an anthracycline/taxane-based chemotherapy in the open-label, multicentre, single-arm phase II study, ‘SOFIA'. <b><i>Patients and Methods: </i></b>Inclusion criteria were: HER2 negative, cT3, cT4 or cT2 cN+, M0 primary breast cancer. Patients received 4 × epirubicin 90 mg/m² and cyclophosphamide 600 mg/m² (EC) intravenously (i.v.) in 3-weekly cycles followed or preceded by 12 weeks of paclitaxel (Pw) 80 mg/m². In cohort 1, sorafenib started at 800 mg daily with chemotherapy. An initial daily sorafenib dose of 200 mg was escalated, based on individual toxicities, every 3 weeks in cohort 2 (starting with EC) and every 2 weeks in cohort 3 (starting with Pw). The primary objective was to identify the most feasible regimen; secondary objectives were safety, pathological complete response (pCR) at surgery and pharmacokinetics. <b><i>Results: </i></b>Of the 36 recruited patients, 7/12 patients completed the study in cohort 1 and 24/24 patients in cohorts 2 and 3. The median cumulative sorafenib dose per patient was 37%, 65% and 46% in cohorts 1, 2 and 3, respectively. The main grade 3-4 toxicities were neutropenia and hand-foot syndrome. The pCR (ypT0/is) rate was 27.7%. No pharmacokinetic interaction was observed between sorafenib and epirubicin. <b><i>Conclusion: </i></b>Sorafenib EC-Pw is feasible if the starting dose is 200 mg, escalated every 3 weeks based on the patients' individual toxicities

Supplementary Material for: Neratinib as extended adjuvant treatment of HER2-positive/HR-positive early breast cancer patients in Germany, Austria and Switzerland: interim results of the prospective, observational ELEANOR study

Introduction: Prognosis of patients diagnosed with HER2+ early breast cancer (eBC) has substantially improved, but distant recurrences impacting quality of life and survival still occur. One treatment option for extended adjuvant treatment in patients with HER2+/HR+ eBC is neratinib; available in Europe for patients who completed adjuvant trastuzumab-based therapy within 1 year. The ELEANOR study is investigating the real-world use of neratinib in Germany, Austria and Switzerland. Results from an interim analysis of the first 200 patients observed for ≥3 months are reported. Methods: The primary objective of this prospective, multicentre, observational study is to assess patient adherence to neratinib (defined as percentage of patients taking neratinib on ≥75% prescribed days). Secondary objectives are patient characteristics and treatment outcomes. Results: At cut-off (May 2, 2022), 202 patients had been observed for ≥3 months, with neratinib treatment documented for 187 patients (median age 53.0 years; 67.9% at increased risk of disease recurrence). In total 151 (80.7%) patients had received prior neoadjuvant treatment; of these 82 (54.3%) achieved a pathological complete response. Neratinib was initiated at a median 3.6 months after trastuzumab-based treatment, with 36.4% starting at a dose <240 mg/day. Treatment is ongoing for 46.0% of patients, with median treatment duration of 11.2 (interquartile range 0.9–12.0) months. Diarrhoea was the most common adverse event (78.6% any grade, 20.3% Grade ≥3); pharmacologic prophylaxis was used in 85.6% of patients. Conclusions: The pattern of anti-HER2 pretreatment observed reflected the current treatment for HER2+/HR+ eBC in Germany, Austria and Switzerland. These interim results suggest that neratinib as an extended adjuvant is a feasible option after various anti-HER2 pretreatments, and that its tolerability can be managed and improved with proactive diarrhoea management. ClinicalTrials.gov identifier: NCT0438838

Supplementary Material for: Factors Influencing Decision-Making for or against Adjuvant and Neoadjuvant Chemotherapy in Postmenopausal Hormone Receptor-Positive Breast Cancer Patients in the EvAluate-TM Study

<i>Background:</i> Decision-making for or against neoadjuvant or adjuvant chemotherapy in postmenopausal patients with hormone receptor-positive breast cancer does not follow any clear guidelines, and some patients may unnecessarily undergo chemotherapy and be exposed to the associated toxicity. The aim of this study was to identify the patient population for whom this issue may bear relevance. <i>Methods:</i>Patients being treated with letrozole in the prospective multicenter noninterventional EvAluate-TM study were recruited. The percentage of patients receiving chemotherapy and factors associated with chemotherapy administration were identified. <i>Results:</i> In all, 3,924 (37.4%) patients received chemotherapy before treatment with letrozole. Of these, 293 (20%) underwent neoadjuvant therapy. Younger age was predictive for both adjuvant and neoadjuvant therapy. Overall, decisions in favor of administering chemotherapy are more likely to be made in patients with a higher body mass index (BMI), and neoadjuvant chemotherapy is administered at a higher rate in women with a lower BMI. Concomitant medication influenced the overall decision-making regarding chemotherapy, irrespective of whether it was given on a neoadjuvant or adjuvant basis. <i>Conclusion:</i> There is an ongoing debate as to whether all of the many patients who receive chemotherapy actually benefit from it. Neoadjuvant chemotherapy is frequently administered in this patient population, and this should encourage further research to resolve current clinical and research issues