Abstract P4-12-08: Final efficacy results from a single-arm multicenter phase II study evaluating first-line trastuzumab, bevacizumab, and capecitabine (HAX) therapy for HER2-positive locally recurrent/metastatic breast cancer (LR/mBC)

Abstract

Abstract Background: After median follow-up of 8.8 months, the primary efficacy results from the HAX study [Martín et al., Oncologist 2012] demonstrated a 73% overall response rate (ORR) according to RECIST (primary endpoint), median progression-free survival (PFS) of 14.4 months and a safety profile typical of the component agents; overall survival (OS) data were immature at that time. We present final efficacy results. Methods: Patients with measurable HER2-positive LR/mBC who had received no prior chemotherapy for LR/mBC received bevacizumab 15 mg/kg day 1, trastuzumab 6 mg/kg day 1 (8 mg/kg loading dose in cycle 1), and capecitabine 1000 mg/m2 bid days 1–14, repeated every 3 weeks until progression, unacceptable toxicity, or withdrawal of consent. Results: At the time of data cut-off, median follow-up was 31.8 months (range 1.2–44.5 months). Median duration of study therapy was 9.0, 9.4, and 10.3 months for bevacizumab, capecitabine, and trastuzumab, respectively. More than 8 cycles were administered in 67%, 65%, and 70%, respectively. Efficacy results in the intent-to-treat population (n = 88) and clinically important subgroups are shown below. Patient subgroupBest ORR,% (95% CI)PFS events, n (%)Median PFS, months (95% CI)Deaths, n (%)Median OS, months (95% CI)1-year OS rate,% (95% CI)All patients (n = 88)75 (65-84)70 (80)14.2 (10.5-14.9)40 (45)31.8 (26.3-38.2)94 (86-98)ER and/or PgR positive (n = 37)73 (56-86)32 (86)14.1 (8.5-17.0)19 (51)31.8 (24.4-42.6)100 (*-*)ER and PgR negative (n = 51)77 (63-87)38 (75)14.5 (10.5-18.9)21 (41)33.1 (23.6-44.5)90 (77-96)No prior chemotherapy (n = 37)81 (65-92)27 (73)14.9 (10.5-24.8)14 (38)31.8 (26.3-44.4)94 (80-99)Prior chemotherapy (n = 51)71 (56-83)43 (84)13.6 (8.5-14.8)26 (51)30.9 (24.3-42.1)94 (82-98)Taxane pretreated (n = 28)57 (37-76)26 (93)9.5 (5.2-14.0)17 (61)27.4 (21.4-33.2)93 (74-98)Prior anti-HER2 therapy (n = 22)73 (50-89)18 (82)12.1 (5.2-17.0)11 (50)30.9 (24.3-*)95 (72-99)Age >60 years (n = 25)72 (51-88)16 (64)14.2 (10.5-21.7)11 (44)33.2 (22.0-*)100 (*-*)*Not reached The most common grade ≥3 adverse events were hand-foot syndrome (26% of patients), diarrhea (11%), and hypertension (11%). The majority of deaths (38/40) were from progressive/underlying disease. The cause of the two remaining deaths was described as unknown; one was reported at the primary analysis and the other occurred 19 months after last study drug administration, following progression. Detailed long-term safety results will be presented. Conclusion: Long-term follow-up results from the HAX study show that this is an active and tolerable first-line triplet therapy for HER2-positive mBC, demonstrating median OS of 31.8 months. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P4-12-08.