HR+/HER2-negative BC represent 70% of all newly diagnosed breast tumours and are responsible
for most recurrences and deaths due to this disease, and despite available standard
therapies, 15-20% of hormone tumours recur at distant sites. As BC is a clinically and
biologically heterogeneous disease, intrincsic subtype may play an important role in
classifying patients. In this case, HER2-E subtype is present in approximately 6.6-11.0% of
HR+/HER2-negative tumors and might express either HER2, estrogen receptor (ER) or
progesterone receptor (PR), we also know that HER2-E is present twice as much in metastatic
tumors compared to primary tumors and that HER2-E patients may benefit in terms of PFS form
an anti-HER2 drug as was showed using retrospective sample in EGF30008 trial. Therefore,
incorporation of novel drugs in combination with endocrine therapy (ET) can improve patient
outcomes in HR+/HER2-negative BC advanced disease specially in those with HER2-E subtype.
Methods NEREA is an open-label, single arm, multicenter phase II study evaluating treatment
with neratinib in combination with ET in pre and post-menopausal women and men with locally
advanced or metastatic HER2-enriched (HER2-E), HR+/HER2-negative breast cancer who had
recurrence or progression while receiving previous ET (either aromatase inhibitors, tamoxifen
or fulvestrant) in the adjuvant setting or to treat advanced disease or both. The study will
follow a Simon's 2-stage design with one interim and one final efficacy analysis. The primary
objective will is assess the efficacy of neratinib in combination with ET is this group of
patients, efficacy will be measured as Progression-Free Survival at 6 months (PFS6) defined
as the proportion of patients alive and without progression, locally assessed by the
investigator through the use of RECIST v.1.1 at 24 weeks after first treatment
administration, imaging evaluation will be performed every 8 weeks for the first 12 months
following treatment start, and every 12 weeks thereafter. Secondary endpoints include
Clinical Benefit Rate at 6 months , Overall Response rate, Duration of response, Time to
response and Incidence, duration and severity of Adverse Events. The interim analysis will be
conducted when 33 patients are evaluable for the primary endpoint having the potential for at
least 3 'on treatment' disease assessment scans. If less than 15 patients achieved a PFS6,
the trial will be terminated for futility in favor of the null hypothesis. If more than 28
patients achieved a PFS6, the trial will be stopped in favor of the alternative hypothesis
demonstrating activity. If none of the two above-mentioned conditions are attain, up to a
further 23 patients may be evaluated, for at least a total of 56 evaluable patients.
Therefore, if a total of 28 or more patients achieved a PFS6 at the end of the second stage,
then the null will be rejected in favor of the alternative.
Eligible patients will receive neratinib 240 mg every day in combination with ET, with either
exemestane, fulvestrant or tamoxifen: exemestane 25 mg every day orally, tamoxifen 20mg every
day orally or fulvestrant 500 mg administered in two intramuscular injections of 250 mg each
at C1D15 and at D1 of each subsequent 28-day cycle at investigator discretion. LHRH agonist
will be used in men and premenopausal women if no oophorectomy has been performed previously.
All patients will take prophylactic loperamide with a stablished doses scheme during the firs
cycle and on demand in subsequent cycles
cancer, breast, Breast Cancer, Breast Cancer Diagnosis, breast carcinoma
If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.
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