PR93612

CASTRES, France, Dec. 10, 2021 /PRNewswire=KYODO JBN/ --

    Today, the final findings of the CONTROL study1 were presented at the 2021

San Antonio Breast Cancer Symposium (SABCS). Results suggest that providing a

prophylactic anti-diarrhoea medical treatment or applying a dose escalation

schedule of neratinib associated with loperamide (as necessary) at treatment

initiation over two-weeks reduces the incidence, severity, and duration of

neratinib-associated grade 3 diarrhoea.  

    The improved tolerability allows HER2+ patients with early breast cancer

(eBC) who have previously been treated with trastuzumab-based therapy within

less than 1 year to stay on neratinib longer, increasing their ability to

receive the full benefit of the therapy.

    The CONTROL study was committed upon the results of the ExteNET pivotal

study2, in which no mandatory anti-diarrhoea therapy was administered and where

grade ≥3 diarrhoea was observed in nearly 40% of patients and 17% of

patients discontinued the study for this specific reason.

    The CONTROL study (n= 563) was designed to investigate six prophylaxis

options for the prevention of neratinib associated diarrhoea. Final results

presented at SABCS determined that adoption of neratinib dose escalation in

association with loperamide (as necessary) during the first two-weeks of

treatment (DE1 cohort) was associated with the lowest rate of grade 3 diarrhoea

during the trial compared with all other investigated anti-diarrheal

strategies. At least 75% of patients received neratinib longer than 11.06

months in the DE1 cohort, compared with 7.46 months in the DE2 cohort, which

comprised of patients taking neratinib over a 4-week escalation and loperamide

(as necessary). The DE1 cohort also reported the lowest rate of

diarrhoea-related discontinuations (3.3%) and dose holds (11.7%).

    Deborah Szafir, Executive Vice President, Medical & Patient Consumer

Department Director said, "The CONTROL study has showed that neratinib

associated diarrhoea can be managed with proactive prophylaxis and dose

escalation strategies. These results provide useful information to the

scientific community about neratinib safety profile and its management. This is

an important outcome as we know that, despite the advances offered by the many

anti-HER2 agents available for early breast cancer treatment, up to 25% of

HER2+ patients will still experience a recurrence of the disease at 10 years."

    The CONTROL study final results were submitted to the European Medicines

Agency in order to align the Product Information with the current scientific

knowledge.

    REFERENCES

    1 Abstract P5-18-02 - Chan A. Final findings from the CONTROL trial of

diarrheal prophylaxis or neratinib dose escalation on neratinib-associated

diarrhea and tolerability in patients with HER2+ early-stage breast cancer –

2021 SABCS, Poster Session 5, Friday, Dec. 10, 7:00-8:30 a.m. CT

    2 Chan A, Delaloge S, Holmes FA, et al. Neratinib after trastuzumab-based

adjuvant therapy in patients with HER2-positive breast cancer (ExteNET): a

multicentre, randomised, double-blind, placebo-controlled, phase 3 trial.

Lancet Oncol. 2016;17:367e377.

    NOTES TO EDITOR

    About CONTROL - NCT02400476

    The CONTROL trial is sponsored by Puma Biotechnology, Inc.. It is an

international, multi-cohort, open-label, phase 2 study designed to investigate

6 preventive antidiarrheal prophylaxis options with loperamide for the

prevention of neratinib associated diarrhoea. Adult patients (563) with stage

I–IIIc HER2+ breast cancer who had completed trastuzumab-based adjuvant therapy

within 1-year prior to study entry received oral neratinib (240 mg/day for 1

year).

    The patients were enrolled sequentially into six separate cohorts:

1.        Mandatory loperamide prophylaxis.

2.        Budesonide + loperamide.

3.        Colestipol + loperamide.

4.        Colestipol + loperamide pro re nata (PRN).

5.        Neratinib DE1 (2-week escalation) + loperamide (PRN, as necessary).

6.        Neratinib DE2 (4-week escalation) + loperamide (PRN, as necessary).

    About ExteNET - NCT00878709

    ExteNET was a multicentre, randomised, double-blind, placebo-controlled

phase III trial. Patients with HER2+ eBC received oral neratinib 240 mg/day or

placebo for 12 months after trastuzumab-based (neo)adjuvant therapy. The

ExteNET trial met its primary endpoint and demonstrated improved invasive

disease-free survival (iDFS) with NERLYNX, compared with placebo in patients

with HER2+ eBC. The greater and more durable efficacy was observed in the

subgroup with HR+ disease who initiated treatment within one year of completing

trastuzumab, referred to as the HR+/≤ 1 year population, leading to the

EMA label population.

    About NERLYNX®

    NERLYNX® (neratinib) is a type of targeted therapy for breast cancer called

an irreversible pan-HER inhibitor (it inhibits HER1, HER2 & HER4). It is a once

daily oral tablets treatment approved in Europe to treat adults with

early-stage human epidermal growth factor receptor 2 positive (HER2+) and

hormone receptor positive (HR+) breast cancer who have previously been treated

with trastuzumab-based therapy within less than 1 year.

    Neratinib works blocking the HER2 receptors on the surface of breast cancer

cells from receiving growth signals and helps to stop the cancer from

spreading.

    NERLYNX® is a registered trademark of Puma Biotechnology, Inc. Puma

in-licenses the global development and commercialization rights to PB272

(neratinib, oral), PB272 (neratinib, intravenous) and PB357.

    Puma granted Pierre Fabre exclusive rights to develop and commercialize

NERLYNX within Europe, Turkey, Middle East, Africa and Greater China.

    For further information, please visit the Pierre Fabre website

at www.pierre-fabre.com, @PierreFabre (https://twitter.com/pierrefabre)

    Contact Pierre Fabre

    Anne Kerveillant  

    anne.kerveillant@pierre-fabre.com

    Logo: https://mma.prnewswire.com/media/1328780/Pierre_Fabre_Logo.jpg

    Source: Pierre Fabre