Background: BCIRG-006 was study designed to assess the relative efficacy and safety of two trastuzumab-based regimens compared to a standard (non-trastuzumab) regimen in the adjuvant treatment of early HER2+ breast cancer. We present the final, protocol-specified analysis of the long-term results from this trial that was initially developed to determine how to maximize adjuvant treatment efficacy and safety in these patients. Material & Methods: Between April, 2001 and March, 2004, we randomized 3,222 HER2+ operable breast cancer patients with axillary lymph node-positive or high risk node-negative disease, to either standard AC (60/600mg/m2 q3wk x 4) followed by T (100mg/m2 q3wk x 4) (AC-T) or two trastuzumab-based regimens. The trastuzumab-based regimens were AC followed by T (100mg/m2 q3wk x 4) and trastuzumab (H) x 1 year (AC-TH), or TCarbo (75mg/m2/AUC6 q3wk x 6) and H x 1 year (TCH). Patients were prospectively stratified by number of positive nodes (0, 1-3 vs ≥4) and hormone receptor status and those with ER and/or PR positive disease received hormone-directed therapy for 5yrs post chemotherapy. The primary endpoint was disease-free survival (DFS). Secondary endpoints included overall survival (OS) and safety, with extensive cardiac evaluation (symptomatic events and asymptomatic, sustained LVEF declines). Results: Baseline characteristics of the study population were well balanced in the three study arms. At a median follow-up of 10.3 years, a persistent significant DFS benefit is seen in both trastuzumab-containing arms compared to AC-T with only 10 DFS events separating the two trastuzumab-based regimens: AC-TH (HR=0.70, 95%CI [0.60, 0.83]; p<0.001)) and TCH (HR=0.76, 95% CI [0.65, 0.90]; p<0.001). At this final analysis, the DFS HRs for AC-TH and TCH are closer than those observed in any prior protocol-directed study analyses (at 5 years follow-up the HRs were 0.64 and 0.75 for AC-TH and TCH respectively). Also, an OS benefit was observed in both AC-TH (HR=0.64, 95% CI [0.52, 0.79]; p<0.001)) and TCH (HR=0.76, 95% CI [0.62, 0.93]; p=0.0081). Importantly, TCH has significantly lower symptomatic CHF events by five-fold compared to AC-TH; 21 (2.0%) for AC-TH vs. 4 (0.4%) for TCH; p=0.0005. The AC-T control arm had 8 (0.8%) symptomatic CHF events. The incidence of patients with a relative LVEF decline >10% is doubled in the AC-TH compared to TCH regimens (206 vs 97; p<0.0001). Discussion: The long-term 10 years final results of the BCIRG 006 trial confirm the significant benefit of trastuzumab in the adjuvant treatment of HER2+ breast cancers, no significant efficacy difference between AC-TH and TCH as well as a significant symptomatic and asymptomatic cardiac safety benefit in the non-anthracycline, TCH trastuzumab-based regimen. Citation Format: Slamon DJ, Eiermann W, Robert NJ, Giermek J, Martin M, Jasiowka M, Mackey JR, Chan A, Liu M-C, Pinter T, Valero V, Falkson C, Fornander T, Shiftan TA, Bensfia S, Hitier S, Xu N, Bée-Munteanu V, Drevot P, Press MF, Crown J, On Behalf of the BCIRG-006 Investigators. Ten year follow-up of BCIRG-006 comparing doxorubicin plus cyclophosphamide followed by docetaxel (AC→T) with doxorubicin plus cyclophosphamide followed by docetaxel and trastuzumab (AC→TH) with docetaxel, carboplatin and trastuzumab (TCH) in HER2+ early breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr S5-04.

These results suggest that TEF is worthy of evaluation as an arm in a phase III trial or as a backbone regimen for new targeted agents in advanced GC. CLINICALTRIALS.GOV: Identifier Trial registration number: NCT00382720.

The results suggest that cabazitaxel has a manageable safety profile in everyday clinical practice. Prophylactic use of G-CSF, especially at cycle 1 and in men aged > or =75 years, is important and improves tolerability in senior adults treated with cabazitaxel.

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ClinicalTrials.gov Identifier NCT00312208.