scholarly journals Position Paper on the Value of Extended Adjuvant Therapy with Neratinib for Early HER2+/HR+ Breast Cancer

Breast Care ◽  
2021 ◽  
pp. 1-13
Author(s):  
Marija Balic ◽  
Gabriel Rinnerthaler ◽  
Rupert Bartsch
Keyword(s):  
Breast Cancer ◽  
Adjuvant Therapy ◽  
Kinase Inhibitor ◽  
Neoadjuvant Treatment ◽  
Unmet Need ◽  
Long Term Outcome ◽  
Risk Of Recurrence ◽  
Her2 Breast Cancer ◽  
Increased Risk ◽  
Extended Adjuvant Therapy

<b><i>Background:</i></b> In August 2018, neratinib – an oral, irreversible pan-HER-tyrosine-kinase inhibitor – was approved by the European Commission for the extended adjuvant treatment of adult patients with early-stage, hormone receptor-positive (HR+), HER2 overexpressed/amplified (HER2+) breast cancer who completed trastuzumab-based adjuvant therapy within the last year. Despite recent improvements in long-term outcome, there is still an unmet need to further reduce the risk of recurrence, especially in patients with poor response to neoadjuvant treatment. <b><i>Summary:</i></b> National and international guidelines included recommendations for using neratinib. Based on the health technology assessment for neratinib, the Federal Joint Committee (G-BA) in Germany has granted an added benefit for neratinib compared with the standard “watch and wait” strategies. Inclusion in the Reimbursement Code, however, was rejected by the Austrian social insurance companies in July 2020, and neratinib is now in the “No Box” for individual head physician reimbursement. <b><i>Key Messages:</i></b> We analysed the value of extended adjuvant therapy with neratinib in early HER2+/HR+ breast cancer based on current data and made recommendations for the evidence-based and economical use of neratinib in Austria. In particular, prognostic factors associated with an increased risk of recurrence following standard therapy are considered. Extended adjuvant therapy should be offered primarily to nodal-positive patients at surgery. For nodal-negative patients, neratinib therapy may be considered in case of large and/or inflammatory primary tumours (T3–4) without pathological complete response after neoadjuvant therapy. For all other patients, neratinib may be considered depending on additional risk factors on an individual basis that should be evaluated by interdisciplinary tumour conferences.

Duration of extended adjuvant therapy with neratinib in early-stage HER2+ breast cancer after trastuzumab-based therapy: Exploratory analyses from the phase III ExteNET trial.

2018 ◽  
Vol 36 (15_suppl) ◽  
pp. 524-524
Author(s):  
Michael Gnant ◽  
Hiroji Iwata ◽  
Anna Elizabeth Bashford ◽  
Robert Separovic ◽  
Adolfo Murias ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Adjuvant Therapy ◽  
Early Stage ◽  
Phase Iii ◽  
Her2 Breast Cancer ◽  
Extended Adjuvant Therapy

Neoadjuvant Treatment of Postmenopausal Breast Cancer With Anastrozole, Tamoxifen, or Both in Combination: The Immediate Preoperative Anastrozole, Tamoxifen, or Combined With Tamoxifen (IMPACT) Multicenter Double-Blind Randomized Trial

2005 ◽  
Vol 23 (22) ◽  
pp. 5108-5116 ◽  
Author(s):  
Ian E. Smith ◽  
Mitch Dowsett ◽  
Stephen R. Ebbs ◽  
J. Michael Dixon ◽  
Anthony Skene ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Adjuvant Therapy ◽  
Postmenopausal Women ◽  
Objective Response ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Operable Breast Cancer ◽  
Her2 Positive ◽  
Long Term Outcome ◽  
Er Positive

Purpose The Immediate Preoperative Anastrozole, Tamoxifen, or Combined With Tamoxifen (IMPACT) trial was designed to test the hypothesis that the clinical and/or biologic effects of neoadjuvant tamoxifen compared with anastrozole and with the combination of tamoxifen and anastrozole before surgery in postmenopausal women with estrogen receptor (ER) –positive, invasive, nonmetastatic breast cancer might predict for outcome in the Arimidex, Tamoxifen Alone or in Combination (ATAC) adjuvant therapy trial. Patients and Methods Postmenopausal women with ER-positive, invasive, nonmetastatic, and operable or locally advanced potentially operable breast cancer were randomly assigned to neoadjuvant tamoxifen (20 mg daily), anastrozole (1 mg daily), or a combination of tamoxifen and anastrozole for 3 months. The tumor objective response (OR) was assessed by both caliper and ultrasound. Comparisons were also made of clinical response with ultrasound response, actual and feasible surgery with feasible surgery at baseline, OR in human epidermal growth factor receptor 2 (HER2) –positive cancers, and tolerability. Results There were no significant differences in OR in the intent-to-treat population between patients receiving tamoxifen, anastrozole, or the combination. In patients who were assessed as requiring mastectomy at baseline (n = 124), 44% of patients received breast-conserving surgery (BCS) after anastrozole compared with 31% of patients after tamoxifen (P = .23); this difference became significant for patients who were deemed feasible for BCS by their surgeon (46% v 22%, respectively; P = .03). The OR for patients with HER2-positive cancer (n = 34) was 58% for anastrozole compared with 22% for tamoxifen (P = .18). All treatments were well tolerated. Conclusion Neoadjuvant anastrozole is as effective and well tolerated as tamoxifen in ER-positive operable breast cancer in postmenopausal women, but the hypothesis that clinical outcome might predict for long-term outcome in adjuvant therapy was not fulfilled.

Neratinib: the emergence of a new player in the management of HER2+ breast cancer brain metastasis

2020 ◽  
Vol 16 (7) ◽  
pp. 247-254 ◽  
Author(s):  
Azadeh Nasrazadani ◽  
Adam Brufsky
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Brain Metastasis ◽  
Kinase Inhibitor ◽  
Metastatic Breast ◽  
Phase Iii ◽  
Breast Cancer Patients ◽  
Her2 Breast Cancer ◽  
Increased Risk ◽  
Breast Cancer Brain Metastasis

HER2-positive (HER2+) breast cancer has become an effectively treatable disease in the era of targeted therapies, and outcomes have improved such that prognosis of this subtype is demonstrated to be superior to HER2-negative disease. Despite these advances, durable responses in HER2+ metastatic disease are challenged by the increased risk for brain metastasis. Neratinib is an irreversible pan-HER kinase inhibitor that has emerged as an effective agent when combined with capecitabine for the management of HER2+ metastatic breast cancer patients with brain metastasis. The randomized, Phase III, NALA trial compares neratinib plus capecitabine to a currently prevailing regimen of lapatinib plus capecitabine and is provided herein. Analysis of NALA portends meaningful changes on the horizon for the management of HER2+ metastatic breast cancer.

The Neat-HER virtual registry: Updated results on HER2+ breast cancer patients receiving neratinib as extended adjuvant therapy.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e13565-e13565
Author(s):  
Gregory A. Vidal ◽  
Debu Tripathy ◽  
Nina Hill ◽  
Deepa Lalla ◽  
Gillian Hanson ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Adjuvant Therapy ◽  
Real World ◽  
Early Stage ◽  
Treatment Patterns ◽  
World Population ◽  
Tumor Characteristics ◽  
Her2 Breast Cancer ◽  
Research Questions ◽  
Extended Adjuvant Therapy

e13565 Background: Data from traditional registries are usually limited to patients treated at study sites. Virtual registries can enroll a broader real-world population. Neat-HER is a U.S.-based virtual registry pilot through PicnicHealth that is enrolling patients with HER2+ breast cancer receiving neratinib as extended adjuvant therapy. Methods: Neat-HER evaluates the feasibility of enrolling patients and answering research questions using a novel electronic platform. Eligibility includes receipt of neratinib in the extended adjuvant setting, signed informed consent for medical record retrieval/data abstraction and age > 18 years. Patients who do not complete enrollment procedures, are participating in a clinical trial or have metastatic disease are excluded. Patients are recruited through multiple mechanisms including private social media groups, treating clinicians and patients enrolled in the Puma Texting Program. Patient health records for breast cancer-related treatment are collected from time of diagnosis to 1-year post-enrollment in the registry. Research questions focus on patient and tumor characteristics, receipt of therapy (e.g. radiotherapy, adjuvant therapy), neratinib duration, and diarrhea prophylaxis. Results: 33 patients with HER2+ early-stage breast cancer who received neratinib as extended adjuvant therapy have been enrolled in this registry study since December 2018. Median age was 50 years, with 79% of patients self-identifying as white. 82% of patients had hormone receptor-positive (ER/PR) disease and 73% of patients had node-positive disease. Prior HER2-targeted adjuvant therapy regimens were as follows: trastuzumab with paclitaxel (9%); trastuzumab/pertuzumab in combination with a taxane(s) (91%). 17 patients (52%) completed 12 months of neratinib treatment; 4 patients (12%) discontinued treatment early; 10 patients (30%) were still ongoing at the time of data cutoff. 31 patients (94%) had diarrhea prophylaxis discussed prior to the start of neratinib treatment. Conclusions: Neat-HER provides useful information on patient/tumor characteristics and treatment patterns in a real-world cohort receiving extended adjuvant neratinib and patient recruitment is ongoing. Updated results show that this pilot virtual registry continues to be a feasible and efficient modality to collect important data on descriptive characteristics and treatment patterns for a patient population derived from real-world practice settings. Validation of this method is needed and could be used in other tumor types.

Effect of prophylaxis on neratinib-associated diarrhea and tolerability in patients with HER2+ early-stage breast cancer: Phase II CONTROL trial.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 548-548 ◽  
Author(s):  
Carlos Hernando Barcenas ◽  
Sara A. Hurvitz ◽  
Jack A. Di Palma ◽  
Ron Bose ◽  
Arlene Chan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Adjuvant Therapy ◽  
Phase Ii ◽  
Dose Escalation ◽  
Kinase Inhibitor ◽  
Early Stage ◽  
Drug Discontinuation ◽  
Entire Treatment Period ◽  
Her2 Breast Cancer ◽  
Grade 3

548 Background: CONTROL (clinicaltrials.gov: NCT02400476) is an open-label, sequential-cohort, phase II study investigating the effectiveness of prophylaxis or dose escalation in preventing diarrhea and improving tolerability of neratinib, an irreversible pan-HER tyrosine kinase inhibitor. Neratinib has demonstrated benefit as an extended adjuvant therapy for early-stage HER2+ breast cancer. Various prophylactic agents are being studied in adult patients treated with oral neratinib (240 mg/day for 1 year) after trastuzumab-based adjuvant therapy. Methods: Patients (n = 485) were enrolled into cohorts investigating antidiarrheal prophylaxis for 1–2 cycles (28 days) with the following agents: loperamide (n = 137); loperamide + budesonide (n = 64); loperamide + colestipol (n = 136); loperamide prn + colestipol (n = 104). An additional cohort assessing loperamide prn + neratinib dose escalation with no mandatory prophylaxis (n = 44) is ongoing. Adverse events were graded according to NCI-CTCAE v4.0. The primary endpoint was incidence of grade ≥3 diarrhea. Data cut-off: 14 Jan 2019. Results: As shown in the table, all prophylactic regimens reduce the incidence of Grade 3 diarrhea and drug discontinuation compared with the prior ExteNET trial [Martin et al. 2017]. The median cumulative duration of Grade 3 or higher diarrhea spanned from 2.0 to 3.5 days across regimens for the entire treatment period. No Grade 4 diarrhea was reported. Conclusions: The addition of budesonide or colestipol to loperamide prophylaxis given for 1–2 cycles reduces the severity and duration of diarrhea in patients treated with neratinib, thereby improving tolerability. Updated data for the dose-escalation cohort will be presented at the meeting. Clinical trial information: NCT02400476. [Table: see text]

scholarly journals De-escalation of radiation therapy in patients with stage I, node-negative, HER2-positive breast cancer

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Jose G. Bazan ◽  
Sachin R. Jhawar ◽  
Daniel Stover ◽  
Ko Un Park ◽  
Sasha Beyer ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Early Stage ◽  
Local Therapy ◽  
Adjuvant Radiation ◽  
Her2 Positive ◽  
Node Negative ◽  
Risk Of Death ◽  
Her2 Breast Cancer ◽  
Neoadjuvant Systemic Therapy ◽  
Increased Risk

AbstractIn the modern era, highly effective anti-HER2 therapy is associated with low local-regional recurrence (LRR) rates for early-stage HER2+ breast cancer raising the question of whether local therapy de-escalation by radiation omission is possible in patients with small-node negative tumors treated with lumpectomy. To evaluate existing data on radiation omission, we used the National Cancer Database (NCDB) to test the hypothesis that RT omission results in equivalent overall survival (OS) in stage 1 (T1N0) HER2+ breast cancer. We excluded patients that received neoadjuvant systemic therapy. We stratified the cohort by receipt of adjuvant radiation. We identified 6897 patients (6388 RT; 509 no RT). Patients that did not receive radiation tended to be ≥70 years-old (odds ratio [OR] = 3.69, 95% CI: 3.02–4.51, p < 0.0001), to have ≥1 comorbidity (OR = 1.33, 95% CI: 1.06–1.68, p = 0.0154), to be Hispanic (OR = 1.49, 95% CI: 1.00–2.22, p = 0.049), and to live in lower income areas (OR = 1.32, 95% CI: 1.07–1.64, p = 0.0266). Radiation omission was associated with a 3.67-fold (95% CI: 2.23–6.02, p < 0.0001) increased risk of death. While other selection biases that influence radiation omission likely persist, these data should give caution to radiation omission in T1N0 HER2+ breast cancer.

scholarly journals Adjuvant Hormonotherapy and Cardiovascular Risk in Post-Menopausal Women with Breast Cancer: A Large Population-Based Cohort Study

Cancers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 2254
Author(s):  
Matteo Franchi ◽  
Roberta Tritto ◽  
Luigi Tarantini ◽  
Alessandro Navazio ◽  
Giovanni Corrao
Keyword(s):  
Breast Cancer ◽  
Heart Failure ◽  
Adjuvant Therapy ◽  
Large Population ◽  
Positive Association ◽  
Population Based ◽  
Study Cohort ◽  
Increased Risk ◽  
Post Menopausal ◽  
New Diagnosis

Background: Whether aromatase inhibitors (AIs) increase the risk of cardiovascular (CV) events, compared to tamoxifen, in women with breast cancer is still debated. We evaluated the association between AI and CV outcomes in a large population-based cohort of breast cancer women. Methods: By using healthcare utilization databases of Lombardy (Italy), we identified women ≥50 years, with new diagnosis of breast cancer between 2009 and 2015, who started adjuvant therapy with either AI or tamoxifen. We estimated the association between exposure to AI and CV outcomes (including myocardial infarction, ischemic stroke, heart failure or any CV event) by a Cox proportional hazard model with inverse probability of treatment and censoring weighting. Results: The study cohort included 26,009 women starting treatment with AI and 7937 with tamoxifen. Over a median follow-up of 5.8 years, a positive association was found between AI and heart failure (Hazard Ratio = 1.20, 95% CI: 1.02 to 1.42) and any CV event (1.14, 1.00 to 1.29). The CV risk increased in women with previous CV risk factors, including hypertension, diabetes and dyslipidemia. Conclusions: Adjuvant therapy with AI in breast cancer women aged more than 50 years is associated with increased risk of heart failure and combined CV events.

scholarly journals Adjuvant therapy for HER2+ breast cancer: practice, perception, and toxicity

2011 ◽  
Vol 131 (2) ◽  
pp. 713-721 ◽  
Author(s):  
Gabrielle Rocque ◽  
Adedayo Onitilo ◽  
Jessica Engel ◽  
Erica Pettke ◽  
Alice Boshoven ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Adjuvant Therapy ◽  
Her2 Breast Cancer

New possibilities of neoadjuvant treatment of ER+ HER2- breast cancer in premenopausal patients

Pharmateca ◽  
2021 ◽  
Vol 7_2021 ◽  
pp. 56-60
Author(s):  
R.V. Orlova Orlova ◽  
A.A. Vakhitova Vakhitova ◽  
M.I. Gluzman Gluzman ◽  
◽  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Treatment ◽  
Her2 Breast Cancer ◽  
Premenopausal Patients
Sign in / Sign up

Export Citation Format

Share Document