Abstract P5-21-17: Efficacy, safety and tolerability of neratinib-based therapy in patients from Asia with metastatic HER2+ breast cancer and other solid tumors: A pooled analysis of 6 clinical trials
Authors: Xu B , Kim S-B , Inoue K , Shen Z-Z , Lee JR , Zhang B , Chow L 
Published: February 2018

Abstract
Background: HER2 overexpression/amplification occurs in ˜15–20% of primary breast cancers (BC) in western populations, although the incidence of HER2+ BC in Asia may be higher (20–44% depending on the country). Neratinib is an irreversible tyrosine kinase inhibitor of HER1, 2 and 4, with demonstrated efficacy in trastuzumab-pretreated and trastuzumab-naïve HER2+ metastatic BC. To better understand the effects of neratinib in Asian patients (pts), we performed a pooled analysis of 6 phase I/II clinical trials in pts with metastatic HER2+ BC or other solid tumors.
Methods: Six prospective phase I/II or II clinical studies of neratinib, alone or in combination with other targeted or chemotherapeutic agents, in pts with metastatic HER2+ BC or other solid tumors were included. A pooled analysis of data from these trials was performed to compare efficacy and safety outcomes with neratinib-based therapy in pts from centers in Asian countries (China, Hong Kong, Japan, Korea, Malaysia, Singapore, and Taiwan) vs pts from other regions (Europe, North/South America, Australasia). Analyses were descriptive in nature. All trials were registered (Clinicaltrials.gov identifiers: NCT00445458; NCT00706030; NCT00398567; NCT00915018; NCT00741260; NCT00300781).
Results: A total of 966 pts were included (Asia, n=329; other regions, n=637). Most pts had HER2+ BC (96.8%); the remaining pts had other solid tumors (3.2%). Baseline characteristics were similar in pts from Asia vs other regions: median age, 52 vs 53 years; ECOG performance status 0/1, 98% vs 97%; hormone receptor-positive, 50% vs 48%. Neratinib was given as monotherapy (n=136) or in combination with paclitaxel (n=352), capecitabine (n=105), vinorelbine (n=91) or trastuzumab (n=45). Median duration of neratinib treatment in pts from Asia vs other regions was 338 vs 213 days; 47.3% vs 26.5% of pts received treatment for &gt;1 year. Efficacy outcomes in pts with HER2+ BC are summarized in the table.
AsiaOther regionsEndpoint(n=239)a(n=435)aORR, n (%)171 (71.5)243 (55.9)CBR, n (%)183 (76.6)275 (63.2)Median PFS (95% CI), weeks56.1 (48.0-67.7)39.3 (32.7-44.1)CBR, clinical benefit rate; ORR, objective response rate; PFS, progression-free survival; a. Excluded phase I, non-BC and non-neratinib–treated pts
Incidence rates of grade 3/4 adverse events (Asia, 62.4% vs other regions, 66.0%) and grade 3/4 diarrhea were similar in both cohorts (25.6% vs 27.2%), but pts from Asia appeared to experience more grade 3/4 hematological events (neutropenia: 21.4% vs 9.8%; leukopenia: 13.0% vs 4.9%). Dose modifications were similar between cohorts, but Asian pts were less likely to withdraw from therapy (2.1% vs other regions, 4.7%).
Conclusions: Asian pts in the pooled metastatic trials appeared to have better ORR, CBR and PFS with neratinib-based therapy than pts from other regions. The safety and tolerability profile of neratinib was broadly similar between regions, except for a higher rate of grade 3/4 hematological events among Asian pts; however, Asian pts were less likely to withdraw from neratinib and stayed on treatment longer, a possible contributing factor to the better clinical outcomes observed in this cohort.
Citation Format: Xu B, Kim S-B, Inoue K, Shen Z-Z, Lee JR, Zhang B, Chow L. Efficacy, safety and tolerability of neratinib-based therapy in patients from Asia with metastatic HER2+ breast cancer and other solid tumors: A pooled analysis of 6 clinical trials [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P5-21-17.