Long-term efficacy analysis of the randomised, phase II TRYPHAENA cardiac safety study: Evaluating pertuzumab and trastuzumab plus standard neoadjuvant anthracycline-containing and anthracycline-free chemotherapy regimens in patients with HER2-positive early breast cancer

Background: We report long-term efficacy and cardiac safety outcomes in patients with HER2-positive early breast cancer treated with neoadjuvant pertuzumab plus trastuzumab with anthracycline-containing or anthracycline-free chemotherapy. Methods: Descriptive efficacy analyses were conducted in patients randomised to group A ( cycles 1-6: trastuzumab [8 mg/kg loading dose and 6 mg/kg maintenance] plus pertuzumab [840 mg loading dose and 420 mg maintenance], plus 5-fluorouracil, epirubicin and cyclophosphamide [FEC] [cycles 1-3; 500 mg/m 2 5-fluorouracil/100 mg/m(2) epirubicin/600 mg/m(2) cyclophosphamide] then docetaxel [cycles 4-6; 75 mg/m(2), escalated to 100 mg/m(2) if well tolerated]), B (cycles 1-3: FEC, cycles 4-6: trastuzumab plus pertuzumab plus docetaxel as mentioned previously) or C (cycles 1-6: trastuzumab plus pertuzumab plus docetaxel [75 mg/m(2), without dose escalation], and carboplatin [AUC 6]), five years after randomisation of the last patient. This study is registered with ClinicalTrials. gov, number NCT00976989. Results: Three-year KaplaneMeier survival estimates for disease-free survival (DFS) were 87% (95% confidence interval: 79-95), 88% (80-96) and 90% (82-97) in groups AeC, respectively. Progression-free survival (PFS) rates were 89% (81-96), 89% (81-96) and 87% (80-95). DFS hazard ratio for total pathological complete response (tpCR) versus no tpCR was 0.27 (0.11-0.64). During post-treatment follow-up, 2/72 (2.8%), 3/75 (4.0%) and 4/76 (5.4%) patients in groups AeC had any-grade left ventricular systolic dysfunction; eight (11.1%), 12 (16.0%) and nine (11.8%) patients experienced left ventricular ejection fraction declines >= 10% from baseline to <50%. Conclusions: Long-term DFS and PFS were similar between groups. Patients who achieved tpCR had improved DFS. No new safety signals were identified. (C) 2017 Elsevier Ltd. All rights reserved.