Analysis of the pan-Asian subgroup of patients in the NALA Trial: a randomized phase III NALA Trial comparing neratinib+capecitabine (N+C) vs lapatinib+capecitabine (L+C) in patients with HER2+metastatic breast cancer (mBC) previously treated with two or more HER2-directed regimens

Abstract

Purpose Neratinib, 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. Methods 621 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. Results 104 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. Conclusion Consistent 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 registration NCT01808573

Cost-effectiveness analysis of neratinib plus capecitabine against lapatinib plus capecitabine for HER2-Positive metastatic breast cancer

“…N + C is an appropriate treatment option for patients with HER2-positive MBC progressing after ≥ 2 lines of HER2-directed treatment. Meanwhile, consistent with the e cacy pro le observed in the overall study population, Asian patients with HER2 + MBC may also bene t from N + C [12].…”

Clinical updates on tyrosine kinase inhibitors in HER2-positive breast cancer

“…The patient’s ORR (overall recovery rate) was 57%, with a PFS of 35.6 weeks. The PFS in both was the same (nine months) ( Dai et al, 2021 ). The ORR for the 19 participants in the study was 63%.…”

“…In the NALA study, neratinib capecitabine significantly outperformed lapatinib capecitabine in terms of PFS and time to intervention for CNS illnesses. For adult patients with metastatic HER2+ who have BC had two or more prior anti-HER2-based regimens in the metastatic setting, the FDA authorised neratinib (in combination with capecitabine) on 25 February 2020 ( Dai et al, 2021 ). The NEfERT-T experiment was split into cohorts 3A (untreated lapatinib) and 3B to reduce the incidence of CNS cancer recurrence (treated lapatinib).…”

“…These two groups had similar outcomes in terms of ORR (clinical benefit rate, and DOR (duration of response) ( Awada et al, 2016 ). Lapatinib plus capecitabine was compared to neratinib plus capecitabine in patients with metastatic HER2-positive BC, who had received at least two prior lines of therapy as part of the Phase 3 NALA trial in patients with metastatic HER2+ BC who had received at least two prior lines of therapy ( Dai et al, 2021 ). Neratinib patients had a better prognosis (hazard ratio 0.76, 95% CI = 0.63–0.93, p = 0.0059) than those in the placebo group.…”

Cost-Effectiveness of Pyrotinib Plus Capecitabine versus Lapatinib Plus Capecitabine for the Treatment of HER2-Positive Metastatic Breast Cancer in China: A Scenario Analysis of Health Insurance Coverage

“…Lapatinib is an orally reversible small molecule, belonging to the tyrosine kinase inhibitor (TKI) family of the target domain of epidermal growth factor receptor (EGFR) and HER2 [ 17 ]. It has been listed as a treatment for HER2-positive BC in China for several years.…”