Trastuzumab use at relapse after adjuvant trastuzumab therapy in HER2-positive breast cancer.

Abstract

575 Background: Trastuzumab (H) is the standard of care for patients with early and advanced HER2-positive breast cancer. It is therefore important to investigate the benefit of retreatment with H for patients who experienced a relapse after adjuvant H. The RHEA trial assessed the efficacy and safety of H plus a taxane, as first-line treatment for patients with metastatic breast cancer (MBC) who relapsed following adjuvant H for HER2-positive early breast cancer. Methods: RHEA was a two-cohort, non-randomized, multicenter, open-label, Phase II study. Patients (N=43) with HER2-positive MBC who had received prior adjuvant H for ≥10 months, with a relapse-free interval of ≥6 months after the last H dose, were recruited. Eligible patients (N=41) were assigned to receive H either weekly (loading dose 4 mg/kg, then 2 mg/kg) or 3-weekly (loading dose 8 mg/kg, then 6 mg/kg) in combination with docetaxel (100 mg/m2 q3w × 6) or paclitaxel (175 mg/m2 q3w × 6 or 75 mg/m2 qw × 18). H was given until progression, unacceptable toxicity, withdrawal or death. Taxanes were given for 18 weeks, with additional cycles at the investigator’s discretion. The primary endpoint was response rate (complete response or partial response) assessed according to RECIST criteria. Results: Patients had a median age of 54 years (range: 31–78) and a median ECOG status of 0 (range: 0–2). Thirty-seven patients received docetaxel, three received paclitaxel and one received nab-paclitaxel. Partial response was observed in 25/41 patients (61%), stable disease in seven patients (17.1%), and progressive disease in six patients (14.6%). Median progression-free survival was 8.0 months (95% CI: 6–11 months). The most common adverse events (AEs, all grades) were alopecia (32%), diarrhea (32%), fatigue (24%), peripheral edema (17%) and asthenia (15%). Six patients (14.6%) developed at least one serious AE. There were no reports of congestive heart failure or any unexpected toxicities. Conclusions: H, in combination with a taxane, is an effective and well tolerated first-line treatment for MBC in patients who relapsed following H-based adjuvant therapy. These data support the concept of retreatment with H in the metastatic setting in patients with HER2-positive BC.