Abstract PD1-07: A Phase 2 study of poziotinib in patients with HER2-positive metastatic breast cancer heavily pre-treated with HER2-targeted therapy
Authors: Brufsky Adam , Zulfiqar Malik , Peguero Julio , Lathrop Kate , Bhat Gajanan , Lebel Francois 
Published: February 2021

Abstract
Background: Poziotinib is a novel pan-HER inhibitor that irreversibly blocks the EGFR family of tyrosine-kinase receptors and inhibits the proliferation of tumor cells. This study evaluates the safety and clinical activity of poziotinib in patients with HER2-positive metastatic breast cancer (MBC) who received at least 2 therapies (trastuzumab and TDM-1) in dose-schedule ranging study. Methods: Patients were treated with oral poziotinib in 2 dose cohorts: 24mg daily 2 weeks/1 week off and 16mg daily continuously in a 21-day cycle. Dose reduction was allowed if toxicity observed. Patients continued treatment until disease progression, death, intolerable AE, or for a maximum of 24 months. The primary endpoint was the objective response rate (ORR), evaluated using RECIST 1.1. Secondary endpoints included disease control rate (DCR), duration of response (DOR), progression-free survival (PFS) and safety.
Results: Sixty-seven patients (33 in 24mg; 34 in 16mg) were enrolled (57 evaluable) in 2 cohorts; all patients either completed or discontinued (36 PD, 5 deaths due to PD, 16 AEs) the study with 1 completed 25 months of treatment. The median (range) age was 57 (29-94) years. Patients were heavily pretreated and the median (range) lines of previous therapy were 7 (2-13) and 4 (2-16) in 2 cohorts respectively [unique drugs 3 (2-5) and 3 (1-9)]; 75% received pertuzumab in addition to trastuzumab and TDM-1 and 37% received at least one tyrosine kinase inhibitor (TKI). The mean relative dose intensity was 57% and 51% with 67% and 47% had dose reductions in 2 cohorts respectively. Common Grade ≥3 treatment-related AEs were similar to other 2nd generation TKIs and include diarrhea (30%), rash (28%) and stomatitis (7%). The ORRs were 27% and 26% with the corresponding median DORs of 5.6 and 13 months respectively. 3 patients in 16mg dose had a CR and another 2 patients had an unconfirmed CR. The DCRs were 50% and 70% in 2 cohorts along with median PFS of 4.1 and 5.8 months respectively. The ORRs were 25% each in 2 cohorts in 24 and 20 heavily pre-treated patients with ≥4 lines of therapy that included trastuzumab, TDM1 and pertuzumab. The ORRs were 23% and 0% in 2 cohorts with 13 and 10 patients received at least one tyrosine kinase inhibitor (TKI) as the sample sizes were small to make any meaningful evaluation.
Conclusion: Poziotinib has demonstrated clinical activity in this dose-ranging study with tumor reduction shown in the majority of patients along with durable responses in this heavily pre-treated MBC patients. Safety profile was mechanism related and was similar to other 2nd generation TKIs.
Citation Format: Adam Brufsky, Malik Zulfiqar, Julio Peguero, Kate Lathrop, Gajanan Bhat, Francois Lebel. A Phase 2 study of poziotinib in patients with HER2-positive metastatic breast cancer heavily pre-treated with HER2-targeted therapy [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PD1-07.