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.

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. 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. 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. 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 P2-16-12: First-Line Bevacizumab Combined with Paclitaxel in Triple-Negative Locally Recurrent/Metastatic Breast Cancer: Subpopulation Analysis of 115 Patients Treated in Routine Oncology Practice in Germany

Abstract Background: Both progression-free survival (PFS) and response rate (RR) are significantly improved when bevacizumab (Bev) is combined with first-line chemotherapy for locally recurrent/metastatic breast cancer (LR/mBC), as demonstrated in three randomized, phase III trials (E2100, AVADO, RIBBON-1). The benefit derived from Bev appears to be similar in triple-negative (TN) and non-TN LR/mBC according to subanalyses of the randomized trials. We conducted a subpopulation analysis of TN patients treated with first-line Bev-paclitaxel (Pac) in a large German observational study in the context of routine oncology practice. Methods: Patients with HER2-negative LR/mBC received first-line Bev-Pac according to the European label at the time of study design. Safety and efficacy data were collected for up to 1 year (or until progression, death, or Bev discontinuation if earlier). The endpoints were safety and efficacy (PFS and RR). We conducted an exploratory analysis of the subset of patients with TN disease. Results: Of the 567 patients for whom data are currently available, 115 (20%) had TN disease. Baseline characteristics and efficacy are summarized below. Overall survival data are immature and follow-up is continuing. Conclusions: In this ongoing study, first-line Bev-Pac demonstrated a 51% RR and median PFS of 7.7 months in patients with TN LR/mBC. These data are consistent with findings from retrospective analyses of randomized phase III trials and a subpopulation analysis of the ATHENA study. Prospective trials evaluating Bev combination regimens in TN breast cancer are ongoing. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P2-16-12.</jats:p

Western Star, 1909-11-10

The Western Star began publication on Newfoundland's west coast on 4 April 1900, appearing weekly with brief semiweekly periods up to 1952, when it became a daily. As of 17 April 2019 it continues as a free weekly community paper

The impact of mammalian target of rapamycin inhibition on bone health in postmenopausal women with hormone receptor-positive advanced breast cancer receiving everolimus plus exemestane in the phase IIIb 4EVER trial

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. Keywords: Bone health, Bone marker, Breast cancer, Everolimus, Hormone receptor-positive, Mammalian target of rapamyci

Abstract P5-19-06: 4EVER - Final efficacy analysis of the phase IIIb, multi-center, open label study for postmenopausal women with estrogen receptor positive locally advanced or metastatic breast cancer (BC) treated with everolimus (EVE) in combination with exemestane (EXE)

Abstract Introduction: The phase III BOLERO-2 trial showed a significant doubling of PFS benefit with EVE + EXE over EXE alone in postmenopausal women with hormone receptor positive advanced BC progressing after non-steroidal aromatase inhibitor (NSAI) therapy. The 4EVER trial further evaluated the combination of EVE+EXE with regard to efficacy and safety, quality of life and health resources utilization in a broader patient population, i.e. without limitations as to the number of previous chemotherapy lines, the time point of progression after NSAI therapy, and the previous EXE therapy. Methods: From May 2012 to November 2012 a total of 299 postmenopausal women with metastatic or locally advanced, hormone receptor positive, HER2 negative breast cancer, refractory to NSAI were recruited to this phase IIIb study. Here we report the results of the planned analysis of the primary and secondary endpoints. The primary endpoint was the overall response rate (ORR) at week 24. The secondary endpoints included: Progression-free survival (PFS), ORR at week 48, overall survival (OS), and quality of life. This study includes a broad exploratory translational research program e.g. changes in serum bone turnover biomarkers, the correlation of Interleukin-6 with anxiety and depression, presence and molecular characteristics of circulating tumor cells, the correlation of response to EXE+EVE with pharmacogenomics. Results: Trial database lock will occur in late June 2014, therefore, the final data concerning the primary and secondary efficacy and safety endpoints will be presented at SACBS 2014. The preliminary baseline analysis included 299 patients (data cut off 15 Nov 2013): HR status: ER+/PgR+ 78.1%, ER+/PgR- 20.9%, 0.7% ER-/PgR+, 0.3% ER-/PgR-. Tissue for receptor status analysis: 71.0% primary tumor, 29.0% metastasis. The mean time since initial diagnosis was 9.6 years, the mean time since first relapse/metastasis was 4.3 years. The mean time since last relapse/metastasis was 2.8 months. 68.1% of patients had bone lesions. Last anti-neoplastic therapy had been administered in the adjuvant (23.9%) and metastatic setting (73.0%). 25.9% of patients had no prior antineoplastic therapy in the metastatic setting, 16.3% had one, 12.2% two and 47.4% three or more prior therapies. Conclusion: The final analysis of the 4EVER study provides more important information on disease patterns and benefits of the combined treatment with EVE and EXE. Citation Format: Hans Tesch, Oliver J Stoetzer, Thomas Decker, Christian M Kurbacher, Romy Neumeister, Frederik Marmé, Andreas Schneeweis, Christoph Mundhenke, Andrea Distelrath, Peter A Fasching, Michael P Lux, Diana Lueftner, Peyman Hadji, Wolfgang Janni, Mathias Muth, Julia Kreuzeder, Claudia Weiss, Diethelm Wallwiener. 4EVER - Final efficacy analysis of the phase IIIb, multi-center, open label study for postmenopausal women with estrogen receptor positive locally advanced or metastatic breast cancer (BC) treated with everolimus (EVE) in combination with exemestane (EXE) [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P5-19-06.</jats:p