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Background: The ExteNET trial demonstrated improved invasive disease-free survival (iDFS) with neratinib, an irreversible pan-HER tyrosine kinase inhibitor, versus placebo in patients with human epidermal growth factor receptor 2-positive (HER2 + )/hormone receptor-positive (HR + ) early-stage breast cancer (eBC)., Patients and Methods: ExteNET was a multicenter, randomized, double-blind, phase III trial of 2840 patients with HER2 + eBC after neoadjuvant/adjuvant trastuzumab-based therapy. Patients were stratified by HR status and randomly assigned 1-year oral neratinib 240 mg/day or placebo. The primary endpoint was iDFS. Descriptive analyses were performed in patients with HR + eBC who initiated treatment ≤ 1 year (HR + /≤ 1-year) and > 1 year (HR + /> 1-year) post-trastuzumab., Results: HR + /≤ 1-year and HR + /> 1-year populations comprised 1334 (neratinib, n = 670; placebo, n = 664) and 297 (neratinib, n = 146; placebo, n = 151) patients, respectively. Absolute iDFS benefits at 5 years were 5.1% in HR + /≤ 1-year (hazard ratio, 0.58; 95% confidence interval [CI], 0.41-0.82) and 1.3% in HR + />1-year (hazard ratio, 0.74; 95% CI, 0.29-1.84). In HR + /≤ 1-year, neratinib was associated with a numerical improvement in overall survival (OS) at 8 years (absolute benefit, 2.1%; hazard ratio, 0.79; 95% CI, 0.55-1.13). Of 354 patients in the HR + /≤ 1-year group who received neoadjuvant therapy, 295 had residual disease, and results showed absolute benefits of 7.4% at 5-year iDFS (hazard ratio, 0.60; 95% CI, 0.33-1.07) and 9.1% at 8-year OS (hazard ratio, 0.47; 95% CI, 0.23-0.92). There were fewer central nervous system events with neratinib. Adverse events were similar to those previously reported., Conclusion: Neratinib significantly improved iDFS in the HER2 + /HR + /≤ 1-year population, and a similar trend was observed in patients with residual disease following neoadjuvant treatment. Numerical improvements in central nervous system events and OS were consistent with iDFS benefits and suggest long-term benefit for neratinib in this population., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

Expression of human epidermal growth factor receptor 2 (HER2) in breast cancer defines a subset of patients (∼15%-20%) who are candidates for anti-HER2 therapies, most notably, trastuzumab, pertuzumab, antibody drug conjugates (eg, T-DM1), and tyrosine kinase inhibitor (TKI) drugs (eg, lapatinib and neratinib), all of which have dramatically changed the prognosis for this aggressive subtype of breast cancer. A roundtable meeting of the Breast Cancer Therapy Expert Group (BCTEG) was convened in March 2018 in an effort to discuss and clarify, from the perspective of the practicing community oncologist, recent developments in the diagnosis and treatment of HER2-positive (HER2 + ) breast cancer. Members of the group selected 4 key topics for discussion prior to the meeting, including diagnosis of HER2 + disease, and its treatment in the neoadjuvant, adjuvant, and metastatic settings. Approved testing methods, such as immunohistochemistry and fluorescence in situ hybridization, are used to demonstrate overexpression and/or amplification of HER2 in breast tumors, and established clinical guidelines are used to appropriately define treatment plans for patients with HER2 + disease. The panel acknowledges a range of treatment options now available for treatment of HER2 + breast cancer in the neoadjuvant, adjuvant, and advanced/metastatic settings, although it is noted that many controversies remain, including the optimal sequence of therapies, the most appropriate treatment(s) for subsets of patients with HER2 + disease (eg, hormone receptor-negative or -positive/HER2 + ), and uncertainties surrounding the diagnosis and definition of HER2 + disease. The current report summarizes the discussion of the BCTEG panel on this topic., (Copyright © 2019. Published by Elsevier Inc.)

Background: Hormonal therapies and single-agent sequential chemotherapeutic regimens are the standards of care for HER2 - metastatic breast cancer (MBC). However, treating patients with hormone-refractory and triple negative (TN) MBC remains challenging. We report the results of combined ixabepilone and carboplatin in a single-arm phase II trial., Patients and Methods: In the present prospective analysis of hormone receptor-positive (HR + )/HER2 - and TN MBC cohorts, patients could have received 0 to 2 chemotherapy regimens for MBC before enrollment. All patients received ixabepilone 20 mg/m 2 and carboplatin (area under the curve, 2.5) on days 1 and 8 every 21 days. The primary endpoint was the objective response rate (ORR). The secondary objectives included progression-free survival (PFS), clinical benefit rate (CBR), overall survival (OS), and toxicity., Results: We enrolled 54 HR + and 49 TN patients (median, 1 previous chemotherapy regimen for metastatic disease; most in addition to adjuvant chemotherapy). The ORR was 34% and 30.4% for the HR + and TN patients, respectively, with a corresponding CBR of 56.6% and 41.3%. The ORRs were similar in taxane-pretreated patients (ORR, 31.4% and 28.6% for HR + and TN patients, respectively). The median OS was 17.9 months for HR + patients and 12.5 months for TN patients. The median PFS was similar for both groups at 7.6 months. Grade 3/4 nonhematologic toxicities included neuropathy (9%) and fatigue (8%). Nine patients developed grade 3/4 neuropathy, 7 of whom had received previous taxane treatment., Conclusion: Ixabepilone plus carboplatin is active even in later-line HR + and TN disease. Toxicities were manageable without cumulative myelosuppression. This combination is a reasonable option for those patients with MBC who require combination chemotherapy., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Adjuvant therapy with aromatase inhibitors is associated with increased bone loss in postmenopausal women with breast cancer. We assessed changes in bone mineral density (BMD) from baseline to 24 months in patients receiving either tamoxifen (T) or exemestane (E)., Patients and Methods: A total of 578 women randomly assigned to T 20 mg per day orally or E 25 mg/day orally enrolled in this substudy; baseline, 12-month, and 24-month BMD measurements of the femur and lumbar spine by dual-energy x-ray absorptiometry were planned. Women receiving bone antiresorptive agents were excluded. Mean BMD changes from baseline to 12 and 24 months were tested between the treatment groups using 2-sample t tests and both g/cm2 (as percent changes) and T scores (as differences from baseline)., Results: A total of 167 women with all 3 imaging studies were evaluable and form the basis of this report (T=89, E=78). Using T scores, the mean difference from baseline was significant between the 2 groups at 12 months at both the spine (P=.0002) and the hip (P=.0004), and at 24 months only at the hip (P=.02)., Conclusion: More bone loss occurred during the first 12 months of treatment with E compared with T, but by 2 years the differences were less apparent and bone loss with E had slowed.

Impaired cognition, fatigue, and diminished quality of life (QOL) are commonly associated with breast cancer chemotherapy. This randomized, double-blind, placebo-controlled pilot trial assessed the feasibility of quantifying the effects of epoetin alfa on cognitive function and mood, and evaluated its effects on fatigue and QOL in patients with breast cancer treated with anthracycline-based adjuvant or neoadjuvant chemotherapy. Patients were randomized to receive epoetin alfa 40,000 U subcutaneously once weekly or placebo at the beginning of 4 cycles of chemotherapy administered over 12 weeks. Cognitive function was assessed by Executive Interview (EXIT25) and Clock Drawing Tasks; mood by Profile of Mood States; anemia-related symptoms, including fatigue, by the Functional Assessment of Cancer Therapy-Anemia (FACT-An) subscale; and QOL by Linear Analog Scale Assessment. Ninety-four patients were evaluable for efficacy and safety. Mean change in EXIT25 scores from baseline to cycle 4 in the epoetin alfa group was 1.3 +/- 3.3; the mean change was 0.3 +/- 2.4 in the placebo group (a negative change indicates improved executive function). There was no difference between groups in mean change in EXIT25 score from baseline to 6-month follow-up assessment. Mean hemoglobin levels were higher in the epoetin alfa group compared with the placebo group after 4 cycles of chemotherapy. Epoetin alfa recipients had less of a decrease in FACT-An subscale scores from baseline to cycle 4 and improvement in FACT-An subscale scores at 6-month follow-up assessment compared with placebo. Epoetin alfa therapy was well tolerated. These data suggest that epoetin alfa may have attenuated the cognitive impairment and fatigue that occurred during adjuvant breast cancer chemotherapy.

Bone pain is a common side effect of treatment with filgrastim. Pegfilgrastim is a pegylated long-acting analogue of filgrastim that is administered once per chemotherapy cycle. The profile of prospectively defined, patient-reported bone pain judged by the investigators as related to study drug was analyzed retrospectively for each drug using data from two comparable phase III trials. These multicenter, randomized, double-blind, noninferiority trials compared once-per-cycle pegfilgrastim (6 mg, study 1 or 100 microg/kg, study 2) to daily filgrastim 5 microg/kg in patients with stage II-IV breast cancer undergoing multiple cycles of myelosuppressive chemotherapy (doxorubicin/docetaxel). Subcutaneous once-per-cycle pegfilgrastim 6-mg and 100-microg/kg doses were administered to 76 and 150 patients, respectively; subcutaneous daily filgrastim 5 microg/kg was administered to a total of 227 patients. Because bone pain in study 1 was higher (P = 0.044) in every cycle compared with study 2, all analyses were performed separately for each study. No statistically significant differences in incidence, severity, or duration were observed between patients receiving either once-per-cycle pegfilgrastim or daily filgrastim in either study. Bone pain incidence and severity were significantly greater (P < 0.001) in cycle 1 of both studies compared with later cycles. Among patients with bone pain, a trend towards earlier onset with pegfilgrastim was observed but was not associated with increased bone pain severity or duration. In patients who received a fixed 6-mg dose of pegfilgrastim, the overall bone pain incidence was similar when analyzed by body weight (< 60 kg, 60-100 kg, > 100 kg). No patients were withdrawn from either study for bone pain.