Abstract P1-18-26: Intracranial efficacy of tucatinib, palbociclib and letrozole combination in patients with HR+/HER2+ breast cancer and brain metastases
Authors: Shagisultanova Elena , Gradishar William , Brown-Glaberman Ursa , Chalasani Pavani , Brenner Andrew , Stopeck Alison , Mayordomo Jose , Diamond Jennifer , Kabos Peter , Borges Virginia F. 
Published: March 2022

Abstract
Background: The phase IB/II clinical trial of tucatinib, palbociclib and letrozole (NCT03054363) showed activity in heavily pretreated patients (pts) with HR+/HER2+ metastatic breast cancer (Shagisultanova et. al, Cancer Res 2021:81(4), PS10-03). Here we report an exploratory analysis of intracranial efficacy in enrolled pts with central nervous system metastases (CNS MTS). Methods: Pts with HR+/HER2+ metastatic breast cancer previously treated with at least 2 HER2-targeted agents were enrolled in this phase IB/II clinical trial. Pts with untreated asymptomatic or treated stable CNS MTS were allowed. Efficacy was assessed using RANO-BM and RECIST1.1 criteria based on investigator assessment. CNS progression free survival (CNS-PFS), defined as intracranial progression or death, and bi-compartmental PFS (CNS and/or non-CNS progression or death) were evaluated; best confirmed CNS responses were summarized. Results: The study enrolled 15 pts with CNS MTS: 2 pts had untreated asymptomatic CNS MTS; 12 patients had treated stable CNS MTS; 1 pt had resection of a solitary CNS MTS prior to initiation of study treatment; this pt subsequently had no evidence of CNS disease for 24 months on study. Among 14 pts with evaluable disease, 13 had stable disease (SD) - 6 for ≥6 months, 7 for &lt;6 months, and 1 pt who had stereotactic radiation to 1.8cm cerebellar lesion prior to enrollment achieved complete response in the CNS after 4 months on study. Among 2pts with untreated CNS lesions, 1pt with non-measurable disease had SD for 5 months on study, and 1pt with measurable disease had SD for 8 months on study. At 6.31.2021 data cutoff and median follow up time of 15 months, median CNS-PFS was 8 months, with 3 out of 15 pts (20%) achieving CNS-PFS of 1 year or greater. Bi-compartmental PFS was 9 months. Among 10 pts who came off study because of PD, 5 had PD in the CNS, 3 had systemic and CNS PD, and 2 had systemic PD. Two pts came off study for reasons other than PD. Three patients are remaining on study with a follow up time of 15, 16 and 28 months. Conclusion: Because the majority of patients had treated (non-target) CNS lesions, evaluation of CNS response was limited and biased towards SD. However, the prolonged CNS-PFS in this small patient subset suggests anti-tumor activity of this non-chemotherapy based targeted regimen in the CNS.
Citation Format: Elena Shagisultanova, William Gradishar, Ursa Brown-Glaberman, Pavani Chalasani, Andrew Brenner, Alison Stopeck, Jose Mayordomo, Jennifer Diamond, Peter Kabos, Virginia F. Borges. Intracranial efficacy of tucatinib, palbociclib and letrozole combination in patients with HR+/HER2+ breast cancer and brain metastases [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-18-26.