Abstract P5-20-01: Prolonged progression-free survival (PFS) in advanced HER2+ metastatic breast cancer with or without brain metastases: A pooled analysis of tucatinib phase 1b studies
Authors: Hamilton E , Murthy R , Ferrario C , Conlin A , Krop I , Falkson C , Khan Q , Chamberlain M , Gray T , Borges V 
Published: February 2018

Abstract
Background: Advances in the treatment for HER2+ breast cancer using sequential HER2 targeted therapies has resulted in improvements in outcome. Nonetheless, treatment of HER2+ metastatic breast cancer (MBC) following 1st and 2nd line HER2 targeted therapies is therapeutically challenging. Currently there is no consensus regarding a single standard of care for such patients including those with brain metastases (BM). Tucatinib is a highly selective oral tyrosine kinase HER2 inhibitor that has shown promising results in the treatment of HER2+ MBC in patients both with and without BM.
Methods: Two Phase 1b studies of tucatinib were pooled to identify and characterize the subgroup of patients with extended PFS as defined by achieving twice the median PFS observed in the trials.
Results: 77 patients treated at the recommended Phase 2 dose (tucatinib 300 mg PO BID) were analyzed, 50 in Study 004 (tucatinib + T-DM1) and 27 in Study 005 (tucatinib +/- trastuzumab +/- capecitabine). Patients received a median of 3 prior therapies including a taxane, trastuzumab, pertuzumab, T-DM1 (Study 005 only), and lapatinib. Median PFS was 8.2 months in Study 004 and 7.8 months in the triplet cohort in Study 005. 15 patients (19.5%) demonstrated PFS &gt;16 months, representing an extended PFS subgroup. Of these patients, 50% had baseline brain metastases, similar to the percentage of all patients entering the trial at baseline. No differences in the incidence of hormone receptor status (positive or negative), presence of visceral metastases, number of prior HER2 regimens, time from diagnosis (initial and metastatic) to study initiation, metastatic disease burden at study entry (LDH, number of target and nontarget lesions, sum of diameters of target lesions) or age were seen when comparing patients with or without extended PFS.
Conclusions: Nearly 20% of patients treated with tucatinib combinations for late stage MBC demonstrate prolonged PFS defined as &gt; 16 months, representing a significant subgroup of patients who have extended disease control. Patient characteristics such as hormone receptor status, presence of visceral disease, burden of disease and age did not predict for extended PFS on tucatinib. While the presence of BM has historically negatively impacted PFS in clinical trials, baseline BM did not differentiate patients who achieved extended PFS. Further molecular characterization of the extended PFS cohort could help to identify this patient group. These data, demonstrating a significant subgroup of patients with extended PFS, further support the use of tucatinib in the accruing randomized HER2CLIMB trial.
Citation Format: Hamilton E, Murthy R, Ferrario C, Conlin A, Krop I, Falkson C, Khan Q, Chamberlain M, Gray T, Borges V. Prolonged progression-free survival (PFS) in advanced HER2+ metastatic breast cancer with or without brain metastases: A pooled analysis of tucatinib phase 1b studies [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 P5-20-01.