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Abstract
PurposeNeratinib, an irreversible pan-HER tyrosine kinase inhibitor, has demonstrated systemic efficacy and intracranial activity in various stages of HER2+breast cancer. NALA was a phase III randomized trial that assessed the efficacy and safety of neratinib+capecitabine (N+C) against lapatinib+capecitabine (L+C) in HER2+ metastatic breast cancer (mBC) patients who had received ≥ 2 HER2-directed regimens. Descriptive analysis results of the Asian subgroup in the NALA study are reported herein.Methods621 centrally assessed HER2+ mBC patients were enrolled, 202 of whom were Asian. Those with stable, asymptomatic brain metastases (BM) were eligible for study entry. Patients were randomized 1:1 to N (240 mg qd) + C (750 mg/m2 bid, day 1–14) with loperamide prophylaxis or to L (1250 mg qd) + C (1000 mg/m2 bid, day 1–14) in 21-day cycles. Co-primary endpoints were centrally assessed progression-free survival (PFS) and overall survival (OS). Secondary endpoints included time to intervention for central nervous system (CNS) disease, objective response rate, duration of response (DoR), clinical benefit rate, and safety.Results104 and 98 Asian patients were randomly assigned to receive N+C or L+C, respectively. Median PFS of N+C and L+C was 7.0 and 5.4 months (P = 0.0011), respectively. Overall cumulative incidence of intervention for CNS disease was lower with N+C (27.9 versus 33.8%; P = 0.039). Both median OS (23.8 versus 18.7 months; P = 0.185) and DoR (11.1 versus 4.2 months; P < 0.0001) were extended with N+C, compared to L+C. The incidences of grade 3/4 treatment emergent adverse events (TEAEs) and TEAEs leading to treatment discontinuation were mostly comparable between the two arms. Diarrhea and palmar-plantar erythrodysesthesia were the most frequent TEAEs in both arms, similar to the overall population in incidence and severity.ConclusionConsistent with the efficacy profile observed in the overall study population, Asian patients with HER2+ mBC, who had received ≥ 2 HER2-directed regimens, may also benefit from N+C. No new safety signals were noted.Clinical trial registrationNCT01808573
Highlights
Breast cancer has been the most prevalent cancer and the leading cause of cancer death among women
Asian patients tend to be younger at disease onset, present with tumors that are estrogen receptor-negative (ER−), human epidermal growth factor receptor 2-positive (HER2+), and have a higher histological grade, compared with their western counterparts [3, 6, 7]
CNS involvement severely compromises the quality of life and prognosis of metastatic breast cancer (mBC) patients, limiting their overall survival (OS) to 30 months [9, 13].While survival of the mBC patients may be extended with trastuzumab, development of central nervous system (CNS) diseases has been shown to be widely inevitable and occurs in around one-third of the mBC patients [8, 14]
Summary
Breast cancer has been the most prevalent cancer and the leading cause of cancer death among women. In 2018, both the newly diagnosed cases and breast cancer deaths in Asia comprised more than 40% of the cases reported globally [1, 3] Such a massive increase has largely been attributed to westernization of lifestyle, as well as enhanced awareness and screening [4]. Asian patients tend to be younger at disease onset, present with tumors that are estrogen receptor-negative (ER−), human epidermal growth factor receptor 2-positive (HER2+), and have a higher histological grade, compared with their western counterparts [3, 6, 7] Most importantly, these features have been identified as important risk factors for brain metastases (BM) in breast cancer patients [8,9,10]. Therapeutic strategies for HER2+ mBC patients following trastuzumab failure are warranted, especially for those with BM
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