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Old 06-14-2015, 12:36 PM   #1
Lani
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Join Date: Mar 2006
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Question Would giving a year of neratinib after completion of chemo& a yr of herceptin prevent

recurrences--how many , at what cost, can we find a way to choose who might benefit and who not?

These are the questions raised by a neratinib study I previously posted from ASCO, but did not sufficiently introduce..

these are the initial findings of a Phase III study

the chemo was giving adjuvantly ( w herceptin) and the entire yr of herceptin completed before the year of neratinib started

neratinib is given for a year AFTER completion of chemo and herceptin


Debra Hughes, MS
June 01, 2015


Neratinib Improves Two-Year Survival in Breast Cancer After Adjuvant Chemo, Trastuzumab



Patients with HER2-positive early-stage breast cancer who received neratinib had improved invasive and ductal carcinoma in situ survival.

CHICAGO—Patients with HER2-positive early-stage breast cancer who received 12 months of neratinib following adjuvant chemotherapy and trastuzumab had improved invasive and ductal carcinoma in situ (DCIS) disease-free survival at 2 years, the phase 3 ExteNET trial concluded at the 2015 American Society of Clinical Oncology (ASCO) Annual Meeting.

“This is the first study intervention to demonstrate a significant improvement in invasive disease-free survival at 2 years,” said Arlene Chan, MB BS, MMed (Palliative Care), Breast Cancer Research Centre - WA & Curtin University in Perth, WA, Australia.

Neratinib, an irreversible pan-HER tyrosine kinase inhibitor, has shown clinical efficacy in patients with HER2-positive metastatic breast cancer who were pretreated with trastuzumab.

Among patients with HER2-positive early breast cancer, a significant proportion of patients recur with invasive disease, despite trastuzumab-containing adjuvant therapy.

Women eligible for the ExteNET trial were those with stage 1 to 3c early breast cancer who received their last dose of trastuzumab less than or equal to 2 years (later modified to stage 2–3c and less than or equal to 1 year) who had locally confirmed HER2-positive disease.

Patients were randomly assigned to oral neratinib 240 mg once daily or placebo for 12 months, stratified by estrogen receptor/progesterone receptor, nodal status, and trastuzumab schedule.

Dr. Chan said a global amendment to the study reduced follow-up to 2 years from study entry; however, a current amendment restored the original 5-year follow-up.

Invasive disease-free survival at 2 years was the primary end point. Secondary end points included DCIS and distant disease-free survival, CNS incidence, and patient-reported outcomes.

Between July 2009 and October 2011, the study investigators randomly assigned 2,821 patients to either neratinib (1,409 patients) or placebo (1,412 patients). Median time from last dose of trastuzumab was 4.4 months in the neratinib arm and 4.7 months in the placebo arm. Baseline characteristics were balanced between arms.

At 2 years, the invasive disease-free survival rate was 93.9% in the neratinib arm and 91.6% in the placebo arm (HR=0.67; 95% CI: 0.50, 0.91; P=0.0009).

The disease-free survival rate was 93.9% compared with 91.0%, respectively (HR=0.63; 95% CI: 0.46, 0.84; P=0.002), and the distant disease-free survival rate was 95.1% compared with 93.7%, respectively (HR=0.75; 95% CI: 0.53, 1.05; one-sided stratified log-rank P=0.0447).

Preplanned subset analyses showed a lower invasive disease-free survival hazard ratio (HR) in estrogen receptor/progesterone receptor-positive patients (1,631 patients; HR=0.51 [0.33–0.77]; P=0.001) and in a centrally confirmed HER2-positive cohort (HR=0.51 [0.33–0.77]; P=0.002).




The most common adverse event (AE) in the neratinib arm was diarrhea; 40% had grade 3 diarrhea and 1 patient had grade 4; however, it primarily occurred within the first 30 days of treatment and was manageable. Dr. Chan recommended intensive prophylaxis with loperamide to reduce the incidence of diarrhea.

Other individual AEs grade 3 or higher occurred in less than 4% of patients in the neratinib arm. Ejection fraction decrease grade 2 or higher was observed in 1.3% of patients in the neratinib arm and 1.1% in the placebo arm.

Mean relative dose intensity was 88% in neratinib-treated patients compared with 98% among those who received placebo.

Additional follow-up will allow assessment of 5-year invasive disease-free and overall survival.

Reference

Chan A, Delaloge S, Holmes FA, et al. Neratinib after adjuvant chemotherapy and trastuzumab in HER2-positive early breast cancer: Primary analysis at 2 years of a phase 3, randomized, placebo-controlled trial (ExteNET). J Clin Oncol. 2015;33suppl; abstr 508).
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Old 07-28-2015, 09:14 AM   #2
forher
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Re: Would giving a year of neratinib after completion of chemo& a yr of herceptin pre

Hi Lani, can you help explain these results? What I'm understanding is that there was not much difference in DFS for both arms of the study. Am I reading this wrong?
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June 2013 DX Stage 3 Idc, rt breast, er/pr-, her2+++
PET/CT/Brain MRI clear
ACTHP until Dec 2013
BMX Dec 2013
28 Rads Feb 2014
Exchange surgery June 2014
Herceptin end Sept 2014
Headaches start Oct 2014
CT body clear Nov 2014
Brain MRI 4 lesions Nov 2014
SRS via LINAC in Dec 2014
Rt side infection, hospitalized, lost right implant on Jan 1, 2015
Jan 14 2015 MRI brain lesions shrinking
Jan 27 2015 Re-start herceptin every 3 weeks
Feb 2015 CT/PET Body clear
Re-start Lymphedema treatment April 2015
Breast MRI clear April 2015
Brain MRI April 2015 - shows everything stable, nothing new (whew)
CT scan June 2015 - clear
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