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

Abstract

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.

The role of irreversible pan-HER tyrosine kinase inhibitors in the treatment of HER2-Positive metastatic breast cancer

“…In line with the previous findings, the most frequent treatment-related AEs for pyrotinib were diarrhea and hand-foot syndrome. Two trials reported that treatment with neratinib plus capecitabine is useful for HER2-positive breast cancer with brain metastases (Cunningham et al, 2022;Pellerino et al, 2022). The results for PFS, OS, and AEs are similar to data from previous trials.…”

“…Pellerino et al (Pellerino et al, 2022) demonstrated that HER2-positive breast cancer patients with leptomeningeal metastases had a 70% probability of receiving a neurological benefit after treatment with neratinib plus capecitabine. Results from the CNS subgroup analysis in NALA (Saura et al, 2020), TBCRC022 (Freedman et al, 2019), and other trials (Hurvitz et al, 2021;Cunningham et al, 2022) also showed that neratinib has an effect on CNS lesions from HER2-positive MBC. The intervention probability for CNS disease was lower in the neratinib group compared to the lapatinib group (cumulative incidence, 22.8% vs 29.2%; p = 0.043)11.…”

Economic evaluation of third-line neratinib plus capecitabine versus lapatinib plus capecitabine with HER2+ metastatic breast cancer

“…Regarding the AEs of neratinib on diarrhea, Cunningham et al. conducted a single-center retrospective study showing that neratinib was well tolerated by most patients as monotherapy or in combination with capecitabine when appropriate anti-diarrhea prophylaxis was given ( 36 ). Therefore, N+C should be considered as a useful alternative in third-line or later treatment of HER2+ mBC disease.…”

Novel 1,2,3-Triazole-Containing Quinoline–Benzimidazole Hybrids: Synthesis, Antiproliferative Activity, In Silico ADME Predictions, and Docking

“…Neratinib, shown in Figure 1, is a quinoline-based therapeutic that acts as a tyrosine kinase inhibitor and is used to treat the early and advanced stages of HER-2 positive breast cancer. It has also been clinically evaluated for the treatment of patients with HER-2 mutated advanced bile duct cancer [28][29][30]. Benzimidazole, also known as 1H-benzimidazole and 1,3-benzodiazole, is an aromatic bicyclic N-heterocycle containing a benzene ring fused to an imidazole ring.…”