NERLYNX

First assessment.

Unfavourable opinion for reimbursement in the extended adjuvant treatment of adult patients with early-stage hormone receptor positive HER2-overexpressed/amplified breast cancer and who completed adjuvant trastuzumab-based therapy less than one year ago.

Role in the care pathway?

The treatment of early breast cancer may be based on surgery, radiotherapy, chemotherapy (neoadjuvant and/or adjuvant) and hormone therapy, depending on the tumour type and grade, axillary lymph node involvement and the existence of hormone receptors.

After surgery, the over-expression of HER2 receptors warrants initiation of systematic adjuvant treatment, irrespective of the stage of the resected tumour. The adjuvant treatment of HER2-positive early breast cancer is generally based on anthracycline-based chemotherapy followed by taxane-based chemotherapy combined with targeted therapy with trastuzumab. Other chemotherapy protocols are sometimes initiated. However, these are systematically combined, either sequentially or concurrently, with trastuzumab treatment. The recommended duration of adjuvant trastuzumab therapy is 12 months.

Role of NERLYNX (neratinib) in the care pathway:

In this context of extended adjuvant treatment and considering:

• the absence of data capable of demonstrating the efficacy of neratinib and assessing the effect size with an adequate level of evidence in the indication validated by the MA,
• the only data available in the MA indication derived from post-hoc exploratory analyses in a subgroup of patients from the ExteNET study, without control of the risk of wrongly concluding that the treatment is effective,
• the poor safety profile of neratinib with increased grade 3 or 4 adverse events (49.7% versus 13.1%) marked by significant gastrointestinal toxicity (diarrhoea: 95.4% versus 35.4%; grade 3 diarrhoea: 39.8% versus 1.6%) as well as hepatotoxicity,

the Committee considers, that as the dossier currently stands, NERLYNX (neratinib) has no role in the extended adjuvant treatment of adult patients with early-stage hormone receptor positive HER2-overexpressed/amplified breast cancer and who completed adjuvant trastuzumab-based therapy less than one year ago.