5-year Analysis of NeoSphere Trial of Pertuzumab Supports Primary Endpoint

A 5-year analysis of the NeoSphere trial supports the primary endpoint of pathological complete response and suggests that neoadjuvant pertuzumab is beneficial when added to trastuzumab and docetaxel, a report published in The Lancet Oncology has shown.¹

The primary analysis of the phase 2 trial demonstrated that combining neoadjuvant pertuzumab with trastuzumab and docetaxel significantly improved pathological complete response. Now, researchers have reported updated analyses of the primary endpoint, as well as 5-year progression-free survival, disease-free survival, and safety.

For the multicenter, open-label study, researchers enrolled 417 treatment-naïve patients with locally advanced, inflammatory, or early-stage human epidermal growth factor receptor 2 (HER2)-positive breast cancer. Participants were randomly assigned 1:1:1:1 to receive 4 neoadjuvant cycles of trastuzumab 6 mg/kg every 3 weeks (8 mg/kg loading dose) plus docetaxel 75 mg/m² every 3 weeks (increasing to 100 mg/m² from cycle 2 if tolerated; group A), pertuzumab 420 mg every 3 weeks (840 mg loading dose) and trastuzumab plus docetaxel (group B), pertuzumab and trastuzumab (group C), or pertuzumab and docetaxel (group D).

Following surgery, patients received fluorouracil 600 mg/m², epirubicin 90 mg/m², and cyclophosphamide 600 mg/m² (FEC) every 3 weeks for 3 cycles (group C received docetaxel for 4 cycles prior to FEC), and trastuzumab 6 mg/kg every 3 weeks to complete 1 year of treatment.

Results showed that  5-year progression-free survival rates were 81% (95% CI, 71-87) for group A, 86% (95% CI, 77-91) for group B, 73% (95% CI, 64-81) for group C, and 73% (95% CI, 63-81) for group D (group B vs group A: HR, 0.69; 95% CI, 0.34-1.40; group C vs group A: HR, 1.25; 95% CI, 0.68-2.30; group D vs group B: HR, 2.05; 95% CI, 1.07-3.93).

Disease-free survival rates were 81% (95% CI, 72-88) for group A, 84% (95% CI, 72-91) for group B, 80% (95% CI, 70-86) for group C, and 75% (95% CI, 64-83) for group D. Researchers also found that patients who achieved total pathological complete response had longer progression-free survival compared with those who did not, suggesting that total pathological complete response could be an early indicator of long-term outcome.

In terms of safety, no new or long-term safety concerns were observed, and tolerability was similar across the 4 treatment arms.

Reference

1. Gianni L, Pienkowski T, Im Y-H, et al. 5-year analysis of neoadjuvant pertuzumab and trastuzumab in patients with locally advanced, inflammatory, or early-stage HER2-positive breast cancer (NeoSphere): a multicentre, open-label, phase 2 randomised trial [published online ahead of print May 11, 2016]. Lancet Oncol. doi: 10.1016/S1470-2045(16)00163-7.