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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 of 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, multicenter, observational study is to assess patient adherence to neratinib (defined as the percentage of patients taking neratinib on ≥75% prescribed days). Secondary objectives are patient characteristics and treatment outcomes. Results: At cut-off (May 2, 2022), a total of 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%) patients achieved a pathologically 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. Diarrhea 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 diarrhea management. [ABSTRACT FROM AUTHOR]

In BOLERO‐2, adding everolimus to exemestane resulted in a twofold increase in median progression‐free survival (PFS) vs exemestane in postmenopausal women with hormone receptor‐positive (HR+), human epidermal growth factor receptor 2‐negative (HER2−) advanced breast cancer (aBC) after progression on a non‐steroidal aromatase inhibitor (NSAI). Here, we report on the open‐label, single‐arm, phase IIIB 4EVER trial (NCT01626222). This trial evaluated the clinical effectiveness of everolimus plus exemestane in postmenopausal women with HR+, HER2− aBC who had progressed on or after an NSAI, but with no restrictions on the time of progression after NSAI, prior chemotherapy for advanced disease or previous exemestane. The primary endpoint was overall response rate (ORR; i.e. the percentage of patients with a best overall response of complete or partial response per RECIST 1.1) within the first 24 weeks of treatment. Secondary endpoints included PFS, overall survival, safety and health‐related quality of life. Between June 2012 and November 2013, 299 patients were enrolled at 82 German centers: 281 patients were evaluable for efficacy and 299 for safety. The ORR was 8.9% (95% confidence interval [CI]: 5.8–12.9%). Median PFS was 5.6 months (95% CI: 5.4–6.0 months). The most frequent grade 3/4 adverse events were stomatitis (8.4%), general physical health deterioration (6.7%), dyspnea (4.7%) and anemia (4.3%). The ORR in 4EVER was lower than in BOLERO‐2, likely due to inclusion of patients with more advanced disease and extensive pretreatment. These data confirm the clinical benefits and known safety profile of everolimus plus exemestane in postmenopausal women with HR+, HER2− aBC. What's new? Current treatment guidelines for HR+, HER2– advanced breast cancer support continued endocrine therapy after progression on first‐line treatment, including the use of everolimus and exemestane combined. Here, the authors report on the phase IIIB 4EVER trial, which evaluated the efficacy, safety and quality of life effects of everolimus plus exemestane in postmenopausal women with pretreated, HR+, HER2– advanced breast cancer. The patient population was broader than that evaluated in previous major trials, and thus more reflective of real‐world practice. Overall, the results confirm the clinical benefits and known safety profile of everolimus plus exemestane in this patient population. [ABSTRACT FROM AUTHOR]

Background/aim: Subcutaneous Herceptin (HER SC) has been shown to be equally effective and safe compared to intravenous Herceptin (HER i.v.) application in early HER2-positive breast cancer (HER2+ BC). However, real-world data from the subcutaneous application are currently limited., Patients and Methods: Based on a non-interventional study (NIS), data from routine clinical use of HER SC have been gathered between 2013 and 2018 in 135 hospitals and open-care practices throughout Germany., Results: A total of 265 patients were recruited in the neo-adjuvant and 605 patients in the adjuvant setting. Primary effectiveness endpoint in the neoadjuvant treatment setting was pathological complete response rate, which was achieved in 41.5%. Primary endpoint in the adjuvant setting was disease free survival rate after 2 years (94.9%). Safety results from the study were comparable to the well-known safety profile of HER i.v. including preferred terms, incidence, severity, including cardiac events. No new safety signals were detected., Conclusion: Effectiveness and safety of HER SC were comparable to data from HER i.v. in early HER2+ BC., (Copyright© 2021, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Breast cancer and its treatments are associated with a detrimental effect on bone health. Here we report the results of an exploratory analysis assessing changes in levels of biomarkers of bone metabolism in patients enrolled in the phase IIIb 4EVER study., Methods: The 4EVER trial investigated everolimus in combination with exemestane in postmenopausal women with hormone receptor-positive, human epidermal growth factor receptor 2-negative locally advanced or metastatic breast cancer. In this prespecified exploratory analysis, changes in biomarkers of bone turnover were assessed in patients from baseline to weeks 4, 12, and 24. The serum bone markers assessed were procollagen type 1 N-terminal propeptide (P1NP), C-terminal cross-linking telopeptide of type 1 collagen (CTX), osteocalcin, parathyroid hormone (PTH), and 25-hydroxyvitamin D (25-OH-vitamin D). On-treatment changes in bone markers over time were described per subgroup of interest and efficacy outcomes., Results: Bone marker data were available for 241 of 299 enrolled patients. At the final assessment, P1NP, osteocalcin, PTH, 25-OH-vitamin D (all P  < 0.001), and CTX ( P  = 0.036) were significantly decreased from baseline values per the Wilcoxon signed-rank test. At the last assessment (24 weeks or earlier), levels of serum CTX and PTH were significantly lower ( P  = 0.009 and P  = 0.034, respectively) among patients with vs. without prior antiresorptive treatment (ART). Serum CTX levels were significantly lower ( P  < 0.001), and 25-OH-vitamin D concentrations significantly higher ( P  = 0.029), at the last postbaseline assessment in patients receiving concomitant ART vs. those without ART. Changes from baseline in PTH and 25-OH-vitamin D concentrations to the final assessment were significantly smaller in patients with prior ART. Lower baseline serum concentrations of osteocalcin and PTH were associated with clinical response (partial vs. non-response) at 24 weeks. High serum levels of CTX and P1NP at baseline were risk factors for progression at 12 weeks., Conclusions: These exploratory analyses support use of everolimus plus exemestane for the treatment of postmenopausal women with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer, and add to the body of evidence suggesting a potentially favorable impact of everolimus on bone turnover., Trial Registration: NCT01626222. Registered 22 June 2012 , https://clinicaltrials.gov/ct2/show/NCT01626222.