Impact of Tucatinib on Progression Free Survival in Patients with HER2+ Metastatic Breast Cancer and Brain Metastases
Session type: E-poster/poster
Tucatinib (TUC), approved in multiple regions for HER2+ metastatic breast cancer (MBC), is a highly selective HER2-directed tyrosine kinase inhibitor with minimal EGFR inhibition. In the pivotal HER2CLIMB trial, TUC added to trastuzumab (T) and capecitabine (C) resulted in statistically significant improvements in PFS and OS in HER2+ MBC patients with and without brain metastases (BM) (Murthy, NEJM 2020). We present exploratory analyses of PFS by type of BM in HER2CLIMB.
HER2CLIMB (NCT02614794) patients were randomized 2:1 to receive TUC or placebo combined with T and C. BM were classified from baseline brain MRI as untreated, treated stable, or treated and progressing. PFS per investigator and OS were analyzed by treatment in stable BM (treated stable) and active BM (untreated + treated progressing), using standard RECIST 1.1 in body and brain.
At baseline, 291 patients (48%) had BM: 198 (48%) with TUC and 93 (46%) with placebo. In stable BM patients (n=117), risk of disease progression or death reduced by 44% with TUC (HR: 0.56; 95% CI: 0.33, 0.96; P=0.03); median (95% CI) PFS was 7.5 months (5.4, 9.6) with TUC vs 5.0 months (2.0, 5.6) with placebo. In active BM (n=174), risk of disease progression or death reduced by 62% with TUC (HR: 0.38; 95% CI: 025, 0.58; P<0.00001); median PFS was 7.6 months (5.7, 8.5) with TUC vs 4.1 months (3.1, 4.3) with placebo. In treated progressing BM patients (n=108), risk of disease progression or death reduced by 64% with TUC (HR: 0.36; 95% CI: 0.21, 0.63; P=0.0002); median PFS was 7.6 months (5.7, 9.6) with TUC vs 4.1 months (3.1, 4.3) with placebo. In untreated BM patients (n=66), risk of disease progression or death reduced by 53% with TUC (HR: 0.47; 95% CI: 0.24, 0.92; P=0.02); median PFS was 6.9 months (5.5, 9.6) with TUC vs 3.6 months (1.5, 7.5) with placebo.
Addition of TUC to T and C significantly improved PFS regardless of BM type, indicating delay of progression in both the body and brain. Patients with active BM (typically excluded from HER2+ MBC trials) had substantially longer PFS with TUC treatment.