In the randomised, controlled, phase 3 trial NeOAdjuvant Herceptin ( NOAH ) trial in women with HER2-positive locally advanced or inflammatory breast cancer, neoadjuvant Trastuzumab ( Herceptin ) has significantly improved pathological complete response rate and event-free survival.
Updated results from primary analysis to establish the long-term benefit of Trastuzumab-containing neoadjuvant therapy, were reported.
This multicentre, open-label, randomised trial in women with HER2-positive locally advanced or inflammatory breast cancer, was done.
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.
The primary endpoint was event-free survival.
Analysis was by intention to treat.
During the period 2002-2005, researchers 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 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% in patients in the Trastuzumab group and 43% 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 ( 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.
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 ).
These results have shown 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. ( Xagena )
Gianni L et al, The Lancet Oncology 2014; 15: 640-647