NeoSphere Shows Possible Pertuzumab PFS Benefit for HER2-positive Breast Cancer

NeoSphere secondary endpoint results shed further light on neoadjuvant pertuzumab for HER2-positive breast cancer patients

medwireNews: Updated NeoSphere results suggest that the addition of neoadjuvant pertuzumab to trastuzumab and docetaxel might improve progression-free survival (PFS) for patients with locally advanced, inflammatory or early-stage HER2-positive breast cancer, although the study is not powered for a formal statistical analysis.

The investigators believe the secondary endpoints of PFS and disease-free survival (DFS) support the phase II trial’s earlier primary endpoint results, which showed a significant increase in the rate of pathological complete response with the triple combination compared with trastuzumab plus docetaxel, pertuzumab plus trastuzumab or pertuzumab plus docetaxel.

Five-year PFS was 86% for 107 patients given pertuzumab, trastuzumab and docetaxel, compared with rates of 81% for the 107 patients given trastuzumab plus docetaxel, and 73% for both the 107 patients given pertuzumab plus trastuzumab and for the 96 patients given pertuzumab plus docetaxel.

And the DFS results for the four treatment groups were “consistent” with the PFS findings, at 84% versus 81%, 80% and 75%, respectively.

However, Luca Gianni, from San Raffaele Cancer Centre in Milan, Italy, and co-investigators acknowledge that wide confidence intervals “allow for the possibility” that pertuzumab, trastuzumab and docetaxel may not be superior to trastuzumab and docetaxel alone.

“The ongoing phase 3 APHINITY trial will assess pertuzumab, in combination with trastuzumab and chemotherapy, in the adjuvant setting”, they comment, providing more information on the efficacy of this combination.

In an accompanying comment, Michael Gnant, Guenther Steger and Rupert Bartsch, from the Medical University of Vienna in Austria, say the NeoSphere findings add an “important piece of information” to the understanding of the link between pathological complete remission and DFS.

Highlighting that 5-year PFS was achieved by 85% of patients with a complete pathological response versus 76% of those who did not meet this endpoint, the commentators say the finding is “reassuring for both patients and clinicians, and strongly suggests that individual total pathological complete remission is a reliable predictor of outcome”.

And noting the large number of trial participants that would be required to demonstrate a significant survival benefit in HER2-positive patients with complete pathological response, they believe that the link between this endpoint and long-term outcome “justifies continuing the quest for increasing pathological complete remission.”


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. Lancet Oncol 2016; Advance online publication 11 May. DOI: 10.1016/S1470-2045(16)00163-7

Gnant M, Steger GG, Bartsch R.  Pathological complete remission and long-term outcome – what do we know in 2016? Lancet Oncol 2016; Advance online publication 11 May. DOI: 10.1016/S1470-2045(16)30038-9

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