293P Impact of tucatinib on progression free survival in patients with HER2+ metastatic breast cancer and stable or active brain metastases

Abstract

Up to 50% of HER2+ metastatic breast cancer (MBC) pts will develop brain metastases (BM) for which effective treatments are needed. In the HER2CLIMB (NCT02614794) double-blind trial, tucatinib (TUC) added to trastuzumab (T) and capecitabine (C) resulted in statistically significant improvements in PFS and OS in HER2+ MBC pts with and without BM (Murthy, NEJM 2019). Risk of disease progression or death in BM pts was 52% lower in the TUC arm vs. the control arm (P<0.001). We present exploratory analyses of PFS by type of BM in HER2CLIMB. HER2CLIMB pts were randomized 2:1 to receive TUC or placebo combined with T and C. All pts had baseline brain MRI. BM were classified as untreated, treated stable, or treated and progressing. PFS per investigator and OS were analyzed by treatment arm in stable BM pts (treated stable) and active BM pts (untreated + treated progressing), using standard RECIST 1.1 assessing disease in both body and brain. At baseline, 291 pts (48%) had BM: 198 (48%) in the TUC arm and 93 (46%) in the control arm. In pts with stable BM (n=117), risk of disease progression or death was reduced by 44% in the TUC arm (HR: 0.56; 95% CI: 0.33, 0.96; P=0.03); median (95% CI) PFS was 7.5 mo (5.4, 9.6) in the TUC arm vs. 5.0 mo (2.0, 5.6) in the control arm. In pts with active BM (n=174), risk of disease progression or death was reduced by 62% in the TUC arm (HR: 0.38; 95% CI: 025, 0.58; P<0.00001); median PFS was 7.6 mo (5.7, 8.5) in the TUC arm vs. 4.1 mo (3.1, 4.3) in the control arm. In pts with treated progressing BM (n=108), risk of disease progression or death was reduced by 64% in the TUC arm (HR: 0.36; 95% CI: 0.21, 0.63; P=0.0002); median PFS was 7.6 mo (5.7, 9.6) in the TUC arm vs. 4.1 mo (3.1, 4.3) in the control arm. In pts with untreated BM (n=66), risk of disease progression or death was reduced by 53% in the TUC arm (HR: 0.47; 95% CI: 0.24, 0.92; P=0.02); median PFS was 6.9 mo (5.5, 9.6) in the TUC arm vs. 3.6 mo (1.5, 7.5) in the control arm. Addition of TUC to T and C significantly improved PFS regardless of BM type, indicating delay of progression not only in the body but also in the brain. Patients with active BM (typically excluded from HER2+ MBC trials) had substantially longer PFS with TUC treatment.