Neratinib safe and effective in Asian HER2-positive metastatic breast cancer patients
Overall, 1,199 patients were included in the seven prospective studies, among which 407 patients were from Asian countries (mainland China: 160 patients; Japan: 121 patients; Korea: 61 patients; Hong Kong: 32 patients; Singapore: 16 patients; Taiwan: ten patients; Malaysia: five patients; Thailand: two patients) and 792 patients from other regions. A total of 793 patients were evaluable for efficacy (Asia: 271 patients; other regions: 522 patients). In patients from Asia, the overall response rate (ORR) with neratinib-based therapy was 66.4 percent and median progression-free survival was 55.6 weeks (95 percent confidence interval, 44.1 to 64.0). [Future Oncol 2019;doi: 10.2217/fon-2019-0222]
The clinical benefit rate among Asian patients was 72.0 percent, while it was 60.2 percent for patients recruited from other regions. The ORR was also lower for patients from other regions, at 51.3 percent.
As the studies included in the analysis were not controlled or matched for this comparison, it is likely that confounding factors were involved. These included the longer duration of neratinib-based therapy among Asian patients; 45 percent of Asian patients received neratinib for at least 1 year vs 25 percent of patients from other regions. “In addition, fewer Asian patients had been pretreated with trastuzumab for metastatic disease than patients from other regions (39 vs 48 percent, respectively),” explained the researchers. “The Asian population was also younger, with a better performance status than the population from other regions,” they added.
All Asian patients with evaluable safety data experienced adverse events (AEs), which were grade 3/4 in 65.6 percent of cases. The most common toxicity associated with neratinib was diarrhoea, which was reported by 96.3 percent of patients. While no grade 4 events were reported, 27.4 percent of patients had grade 3 diarrhoea. “Many of the other common toxicities reported (i.e., neutropenia, leukopenia, palmar–plantar erythrodysesthesia, alopecia, peripheral sensory neuropathy and stomatitis) were related to the chemotherapy component of study treatment rather than neratinib, as these events are either uncommon or not observed with neratinib monotherapy,” noted the researchers. [Lancet Oncol 2016;17:367–377]
Neratinib was discontinued by 23.3 percent of Asian patients due to AEs, while neratinib dose reductions had to be implemented in 31.9 percent of cases. An improved understanding of the pattern of diarrhoeal events with neratinib has led to the use of a prophylactic regimen of high-dose loperamide for the first one to two cycles of therapy, which was not mandated in most of the studies included in present analysis. [J Clin Oncol 2019;37:abstract 548]. “As the studies included in our analysis predate the introduction of loperamide prophylaxis, it is anticipated that lower rates of diarrhoea may be expected in Asian patients with its use than are reported here,” commented the researchers.
“At the time the studies included in our analysis were performed, trastuzumab in combination with a taxane was the preferred first-line regimen for HER2-positive metastatic breast cancer. Almost half of the patients included in our analysis had received prior trastuzumab, and our data provide support for the clinical activity of neratinib in trastuzumab-pretreated patients,” concluded the researchers.