TY - JOUR
T1 - HannaH phase III randomised study
T2 - Association of total pathological complete response with event-free survival in HER2-positive early breast cancer treated with neoadjuvant-adjuvant trastuzumab after 2 years of treatment-free follow-up
AU - Jackisch, Christian
AU - Hegg, Roberto
AU - Stroyakovskiy, Daniil
AU - Ahn, Jin Seok
AU - Melichar, Bohuslav
AU - Chen, Shin Cheh
AU - Kim, Sung Bae
AU - Lichinitser, Mikhail
AU - Starosławska, Elzbieta
AU - Kunz, Georg
AU - Falcon, Silvia
AU - Chen, Shou Tung
AU - Crepelle-Fléchais, Aulde
AU - Heinzmann, Dominik
AU - Shing, Mona
AU - Pivot, Xavier
N1 - Publisher Copyright:
© 2016 The Author(s). Published by Elsevier Ltd.
PY - 2016/7/1
Y1 - 2016/7/1
N2 - Background In the phase III, open-label, randomised HannaH study, fixed-dose neoadjuvant-adjuvant subcutaneous trastuzumab for human epidermal growth factor receptor 2 (HER2)-positive early breast cancer was non-inferior to standard weight-based intravenous infusion in terms of serum trough concentration and pathological complete response (PCR). Evidence suggests that PCR, particularly total PCR (tPCR), is likely to predict clinical benefit. We report associations between tPCR and event-free survival (EFS) from HannaH (the largest population from a single study of patients presenting with newly diagnosed HER2-positive breast cancer treated with neoadjuvant-adjuvant trastuzumab to date) plus long-term efficacy and safety. Methods Eligible patients received four cycles of neoadjuvant docetaxel followed by four cycles of fluorouracil/epirubicin/cyclophosphamide administered concurrently with 3-weekly subcutaneous (600 mg fixed dose) or intravenous trastuzumab (8 mg/kg loading, 6 mg/kg maintenance doses). Post-surgery, patients received adjuvant trastuzumab as randomised to complete 1 year of standard treatment. In exploratory analyses, we used Cox regression to assess associations between tPCR and EFS. EFS rates per subgroup were estimated using the Kaplan-Meier method. Findings Three-year EFS rates were 76% for subcutaneous and 73% for intravenous trastuzumab (unstratified hazard ratio [HR] 0.95, 95% confidence interval [CI] 0.69-1.30; intention-to-treat population). Three-year overall survival rates were 92% for subcutaneous and 90% for intravenous trastuzumab (unstratified HR 0.76, 95% CI 0.44-1.32). tPCR was associated with a reduced risk of an EFS event: subcutaneous arm HR 0.38 (95% CI 0.22-0.65); intravenous arm HR 0.32 (95% CI 0.18-0.60). Results were similar for subgroups, including oestrogen receptor status. The few additional adverse events occurring during treatment-free follow-up were balanced between arms. Interpretation Long-term efficacy supports the established non-inferiority of subcutaneous trastuzumab, and its safety profile remains consistent with the known intravenous profile. In each of HannaH's treatment arms, tPCR was associated with improved EFS, adding to evidence that tPCR is associated with clinical benefit in HER2-positive early breast cancer.
AB - Background In the phase III, open-label, randomised HannaH study, fixed-dose neoadjuvant-adjuvant subcutaneous trastuzumab for human epidermal growth factor receptor 2 (HER2)-positive early breast cancer was non-inferior to standard weight-based intravenous infusion in terms of serum trough concentration and pathological complete response (PCR). Evidence suggests that PCR, particularly total PCR (tPCR), is likely to predict clinical benefit. We report associations between tPCR and event-free survival (EFS) from HannaH (the largest population from a single study of patients presenting with newly diagnosed HER2-positive breast cancer treated with neoadjuvant-adjuvant trastuzumab to date) plus long-term efficacy and safety. Methods Eligible patients received four cycles of neoadjuvant docetaxel followed by four cycles of fluorouracil/epirubicin/cyclophosphamide administered concurrently with 3-weekly subcutaneous (600 mg fixed dose) or intravenous trastuzumab (8 mg/kg loading, 6 mg/kg maintenance doses). Post-surgery, patients received adjuvant trastuzumab as randomised to complete 1 year of standard treatment. In exploratory analyses, we used Cox regression to assess associations between tPCR and EFS. EFS rates per subgroup were estimated using the Kaplan-Meier method. Findings Three-year EFS rates were 76% for subcutaneous and 73% for intravenous trastuzumab (unstratified hazard ratio [HR] 0.95, 95% confidence interval [CI] 0.69-1.30; intention-to-treat population). Three-year overall survival rates were 92% for subcutaneous and 90% for intravenous trastuzumab (unstratified HR 0.76, 95% CI 0.44-1.32). tPCR was associated with a reduced risk of an EFS event: subcutaneous arm HR 0.38 (95% CI 0.22-0.65); intravenous arm HR 0.32 (95% CI 0.18-0.60). Results were similar for subgroups, including oestrogen receptor status. The few additional adverse events occurring during treatment-free follow-up were balanced between arms. Interpretation Long-term efficacy supports the established non-inferiority of subcutaneous trastuzumab, and its safety profile remains consistent with the known intravenous profile. In each of HannaH's treatment arms, tPCR was associated with improved EFS, adding to evidence that tPCR is associated with clinical benefit in HER2-positive early breast cancer.
KW - Herceptin
KW - Neoadjuvant chemotherapy
KW - Pathological complete response
KW - Subcutaneous
KW - Trastuzumab
UR - http://www.scopus.com/inward/record.url?scp=84969247875&partnerID=8YFLogxK
U2 - 10.1016/j.ejca.2016.03.087
DO - 10.1016/j.ejca.2016.03.087
M3 - 文章
C2 - 27208905
AN - SCOPUS:84969247875
SN - 0959-8049
VL - 62
SP - 62
EP - 75
JO - European Journal of Cancer
JF - European Journal of Cancer
ER -