Phase II study of MEK inhibitor trametinib alone and in combination with AKT inhibitor GSK2141795/uprosertib in patients with metastatic triple negative breast cancer.
Document Type
Article
Publication Title
Breast cancer research and treatment
Abstract
PURPOSE: While MEK inhibitors demonstrated activity in metastatic triple negative breast cancer (mTNBC) preclinical studies, preclinical, and clinical studies implicate rapid development of resistance limiting clinical benefit. The purpose of this study was to determine response rate for Trametinib alone and in combination with Uprosertib in patients with mTNBC previously treated with chemotherapy.
METHODS: This was an open-label, two-part, phase II, single-arm, multicenter study. Patients first received Trametinib monotherapy (2 mg daily; Part I) then at progression transitioned to Trametinib (1.5 mg) plus Uprosertib (50 mg; Part II).
RESULTS: Between October 2013 and January 2017, 37 patients were enrolled to Part I. Subsequently, 19 patients entered Part II. Of the 37 patients receiving Trametinib monotherapy, 2 patients achieved partial response (PR) for an ORR of 5.4% (2/37) and an additional 6/37 (16.2%) achieved stable disease (SD). The clinical benefit rate (PR+SD) for patients receiving monotherapy was 21.6% (8/37). Of the 19 patients in Part II, 3 patients achieved PR for an ORR to Part II of 15.8% (3/19) and an additional 3 achieved SD. Median progression-free survival (PFS) was 7.7 weeks for Part I and 7.8 weeks for Part II. Circulating tumor DNA (ctDNA) clearance at C2D1 of Trametinib monotherapy was associated with improved PFS and overall survival.
CONCLUSION: In patients with mTNBC, Trametinib monotherapy demonstrated limited efficacy and addition of Uprosertib was associated with numerically greater objective responses but no difference in PFS. Translational analyses suggest ctDNA clearance as a potential early biomarker of response.
First Page
179
Last Page
189
DOI
10.1007/s10549-024-07551-z
Publication Date
2-1-2025
Recommended Citation
Prasath, Vishnu; Boutrid, Hinda; Wesolowski, Robert; Abdel-Rasoul, Mahmoud; Timmers, Cynthia; Lustberg, Maryam; Layman, Rachel M; Macrae, Erin; Mrozek, Ewa; Shapiro, Charles; Glover, Kristyn; Vater, Mark; Budd, G Thomas; Harris, Lyndsay; Isaacs, Claudine; Dees, Claire; Perou, Charles M; Johnson, Gary L; Poklepovic, Andrew; Chen, Helen; Villalona-Calero, Miguel; Carson, William; Stover, Daniel G; and Ramaswamy, Bhuvaneswari, "Phase II study of MEK inhibitor trametinib alone and in combination with AKT inhibitor GSK2141795/uprosertib in patients with metastatic triple negative breast cancer." (2025). Oncology Articles. 35.
https://scholarlyworks.ohiohealth.com/oncology-articles/35
