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 pa...

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Main Authors: Schneeweiss, Andreas (Author) , Chia, Stephen (Author) , Hickish, Tamas (Author) , Harvey, Vernon (Author) , Eniu, Alexandru (Author) , Waldron-Lynch, Maeve (Author) , Eng-Wong, Jennifer (Author) , Kirk, Sarah (Author) , Cortes, Javier (Author)
Format: Article (Journal)
Language:English
Published: January 2018
In: European journal of cancer
Year: 2018, Volume: 89, Pages: 27-35
ISSN:1879-0852
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Author Notes:Andreas Schneeweiss, Stephen Chia, Tamas Hickish, Vernon Harvey, Alexandru Eniu, Maeve Waldron-Lynch, Jennifer Eng-Wong, Sarah Kirk, Javier Cortés
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Summary: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/m2 5-fluorouracil/100 mg/m2 epirubicin/600 mg/m2 cyclophosphamide] then docetaxel [cycles 4-6; 75 mg/m2, escalated to 100 mg/m2 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/m2, 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 Kaplan-Meier survival estimates for disease-free survival (DFS) were 87% (95% confidence interval: 79-95), 88% (80-96) and 90% (82-97) in groups A-C, 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 A-C 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.
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ISSN:1879-0852