Neoadjuvant and adjuvant trastuzumab in patients with HER2-positive locally advanced breast cancer (NOAH): follow-up of a randomised controlled superiority trial with a parallel HER2-negative cohort

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• 作者：Dr Luca Gianni ; MD^a ; ^{gianni.luca@hsr.it" class="auth_mail} ; Wolfgang Eiermann ; MD^b ; Vladimir Semiglazov ; MD^c ; Ana Lluch ; PhD^d ; Sergei Tjulandin ; MD^e ; Milvia Zambetti ; MD^a ; Angela Moliterni ; MD^f ; Federico Vazquez ; MD^g ; Mikhail J Byakhov ; PhD^h ; Mikhail Lichinitser ; MD^e ; Miguel Angel Climent ; MDⁱ ; Eva Ciruelos ; MD^j ; Belen Ojeda ; MD^k ; Mauro Mansutti ; MD^l ; Alla Bozhok ; PhD^c ; Domenico Magazzù ; PhD^m ; Dominik Heinzmann ; PhDⁿ ; Jutta Steinseifer ; PhDⁿ ; Pinuccia Valagussa ; BS^m ; Jose Baselga ; MD^o
• 刊名：Lancet Oncology
• 出版年：May 2014
• 年：2014
• 卷：15
• 期：6
• 页码：640-647
• 全文大小：294 K

文摘

In our randomised, controlled, phase 3 trial NeOAdjuvant Herceptin (NOAH) trial in women with HER2-positive locally advanced or inflammatory breast cancer, neoadjuvant trastuzumab significantly improved pathological complete response rate and event-free survival. We report updated results from our primary analysis to establish the long-term benefit of trastuzumab-containing neoadjuvant therapy.

Methods

We did this multicentre, open-label, randomised trial in women with HER2-positive locally advanced or inflammatory breast cancer. Participants were randomly assigned (1:1), by computer program with a minimisation technique, to receive neoadjuvant chemotherapy alone or with 1 year of trastuzumab (concurrently with neoadjuvant chemotherapy and continued after surgery). A parallel group with HER2-negative disease was included and received neoadjuvant chemotherapy alone. Our primary endpoint was event-free survival. Analysis was by intention to treat. This study is registered at www.controlled-trials.com, ISRCTN86043495.

Findings

Between June 20, 2002, and Dec 12, 2005, we enrolled 235 patients with HER2-positive disease, of whom 118 received chemotherapy alone and 117 received chemotherapy plus trastuzumab. 99 additional patients with HER2-negative disease were included in the parallel cohort. After a median follow-up of 5·4 years (IQR 3·1–6·8) the event-free-survival benefit from the addition of trastuzumab to chemotherapy was maintained in patients with HER2-positive disease. 5 year event-free survival was 58% (95% CI 48–66) in patients in the trastuzumab group and 43% (34–52) in those in the chemotherapy group; the unadjusted hazard ratio (HR) for event-free survival between the two randomised HER2-positive treatment groups was 0·64 (95% CI 0·44–0·93; two-sided log-rank p=0·016). Event-free survival was strongly associated with pathological complete remission in patients given trastuzumab. Of the 68 patients with a pathological complete response (45 with trastuzumab and 23 with chemotherapy alone), the HR for event-free survival between those with and without trastuzumab was 0·29 (95% CI 0·11–0·78). During follow-up only four cardiovascular adverse events were regarded by the investigator to be drug-related (grade 2 lymphostasis and grade 2 lymphoedema, each in one patient in the trastuzumab group, and grade 2 thrombosis and grade 2 deep vein thrombosis, each in one patient in the chemotherapy-alone group).

Interpretation

These results show a sustained benefit in event-free survival from trastuzumab-containing neoadjuvant therapy followed by adjuvant trastuzumab in patients with locally advanced or inflammatory breast cancer, and provide new insight into the association between pathological complete remission and long-term outcomes in HER2-positive disease.

Funding

F Hoffmann-La Roche.