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 seque...
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