Neratinib as extended adjuvant therapy in patients with copositive early breast cancer: German health technology assessment-driven analyses from the ExteNET study

Eur J Cancer. 2021 Jun:150:268-277. doi: 10.1016/j.ejca.2021.03.045. Epub 2021 May 7.

Abstract

Background: Neratinib is approved in the European Union for extended adjuvant treatment of human epidermal growth factor receptor 2-positive/hormone receptor-positive (copositive) early breast cancer ≤1 year of completion of prior trastuzumab-based therapy. Here, we report analyses of the hormone receptor-positive subgroup (N = 1631) from the ExteNET trial performed for the German health technology assessment (HTA).

Results: With 2 years of median follow-up, HTA analyses revealed a significant advantage in disease-free survival (DFS) for neratinib vs. placebo (absolute/relative risk reduction: 4.1/48.2%; hazard ratio [HR] [95% confidence interval {CI}]: 0.45 [0.29; 0.69]; p = 0.0002), consistent with distant DFS (absolute/relative risk reduction: 3.1/46.3%; HR [95% CI]: 0.52 [0.32; 0.84]; p = 0.0082). The 5-year follow-up confirmed this outcome.Quality of life analyses did not show clinically relevant differences over all time points. Only at month 1, the Functional Assessment of Cancer Therapy - General total score revealed a statistically relevant difference to the disadvantage of neratinib classified as clinically relevant. The tolerability profile of neratinib was dominated by gastrointestinal events, mainly diarrhoea (all grades: 94.4%; grade III: 39.4%; no systematic antidiarrhoeal prophylaxis), nausea (all grades/grade III: 43.9/1.6%), vomiting (26.6/3.2%), abdominal pain (23.8/1.9%), fatigue (28.1/1.9%) and rash (14.3/0.4%). No cumulative or irreversible toxicities were observed. As shown in the CONTROL study and instituted via a risk management plan, diarrhoea management can reduce frequency, cumulative duration and severity of diarrhoea.

Conclusion: Extended adjuvant neratinib provides a clinically relevant benefit with further incremental reduction of relapse risk in the curative setting. Accordingly, the German HTA authority has granted an added benefit for this new treatment option.

Keywords: Breast cancer; Copositive; Extended adjuvant treatment; HER2-positive; Hormone receptor–positive; Neratinib; Triple-positive.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antidiarrheals / administration & dosage
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / adverse effects
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / mortality
  • Breast Neoplasms / pathology
  • Chemotherapy, Adjuvant
  • Clinical Trials, Phase III as Topic
  • Diarrhea / chemically induced
  • Diarrhea / prevention & control
  • Disease-Free Survival
  • Drug Administration Schedule
  • Female
  • Germany
  • Humans
  • Middle Aged
  • Protein Kinase Inhibitors / administration & dosage*
  • Protein Kinase Inhibitors / adverse effects
  • Quality of Life
  • Quinolines / administration & dosage*
  • Quinolines / adverse effects
  • Randomized Controlled Trials as Topic
  • Risk Assessment
  • Risk Factors
  • Technology Assessment, Biomedical*
  • Time Factors
  • Young Adult

Substances

  • Antidiarrheals
  • Antineoplastic Agents
  • Protein Kinase Inhibitors
  • Quinolines
  • neratinib