Neratinib in advanced HER2-positive breast cancer: experience from the royal Marsden hospital

Purpose To describe the tolerability and efficacy of neratinib as a monotherapy and in combination with capecitabine in advanced HER2-positive breast cancer in a real-world setting. Methods Patients who received neratinib for advanced HER2-positive at the Royal Marsden Hospital NHS Trust between August 2016 and May 2020 were identified from electronic patient records and baseline characteristics, previous treatment and response to treatment were recorded. The primary endpoint of the study was progression-free survival (PFS). Secondary endpoints included overall survival (OS) and safety. Results Seventy-two patients were eligible for the analysis. Forty-five patients received neratinib in combination with capecitabine and 27 patients received monotherapy. After a median duration of follow-up of 38.5 months, the median PFS for all patients was 5.9 months (95% confidence interval (CI) 4.9–7.4 months) and median OS was 15.0 months (95% Cl 10.4–22.2 months). Amongst the 52.7% (38/72) patients with confirmed brain metastases at baseline, median PFS was 5.7 months (95% CI 2.9–7.4 months) and median OS was 12.5 months (95% CI 7.7–21.4 months). Despite anti-diarrhoeal prophylaxis, diarrhoea was the most frequent adverse event, reported in 64% of patients which was grade 3 in 10%. There were no grade 4 or 5 toxicities. Seven patients discontinued neratinib due to toxicity. Conclusions Neratinib monotherapy or in combination with capecitabine is a useful treatment for patients with and without brain metastases. PFS and OS were found to be similar as previous trial data. Routine anti-diarrhoeal prophylaxis allows this combination to be safely delivered to patients in a real-world setting.