Efficacy of Anti-HER2 Agents in Combination With Adjuvant or Neoadjuvant Chemotherapy for Early and Locally Advanced HER2-Positive Breast Cancer Patients: A Network Meta-Analysis.

Márcio Debiasi,Rodrigo S Guindalini,Carlos Barrios,Hongyuan Cao,Patrícia Ziegelmann,Dianne M Finkelstein,James J Dignam,Paul Goss,Caroline Albuquerque,Paulo Filho,Brittany Bychkovsky,Olufunmilayo Olopade,Evandro De Azambuja,Carisi A Polanczyk,Tomás Reinert

doi:10.3389/fonc.2018.00156

Abstract

Several (neo)adjuvant treatments for patients with HER2-positive breast cancer have been compared in different randomized clinical trials. Since it is not feasible to conduct adequate pairwise comparative trials of all these therapeutic options, network meta-analysis offers an opportunity for more detailed inference for evidence-based therapy. Phase II/III randomized clinical trials comparing two or more different (neo)adjuvant treatments for HER2-positive breast cancer patients were included. Relative treatment effects were pooled in two separate network meta-analyses for overall survival (OS) and disease-free survival (DFS). 17 clinical trials met our eligibility criteria. Two different networks of trials were created based on the availability of the outcomes: OS network (15 trials: 37,837 patients); and DFS network (17 trials: 40,992 patients). Two studies-the ExteNET and the NeoSphere trials-were included only in this DFS network because OS data have not yet been reported. The concept of the dual anti-HER2 blockade proved to be the best option in terms of OS and DFS. Chemotherapy (CT) plus trastuzumab (T) and lapatinib (L) and CT + T + Pertuzumab (P) are probably the best treatment options in terms of OS, with 62.47% and 22.06%, respectively. In the DFS network, CT + T + Neratinib (N) was the best treatment option with 50.55%, followed by CT + T + P (26.59%) and CT + T + L (20.62%). This network meta-analysis suggests that dual anti-HER2 blockade with trastuzumab plus either lapatinib or pertuzumab are probably the best treatment options in the (neo)adjuvant setting for HER2-positive breast cancer patients in terms of OS gain. Mature OS results are still expected for the Aphinity trial and for the sequential use of trastuzumab followed by neratinib, the treatment that showed the best performance in terms of DFS in our analysis.

Highlights

Breast cancer is the most common malignancy among women worldwide accounting for 2.4 million new cases and 523,000 deaths yearly [1]
Within the current context of personalized medicine, where physicians and policy makers must base their decisions on the highest level of available evidence in order to choose one out of multiple available treatment options, the present study aims to summarize the network of evidence supporting the treatment of patients with early and locally advanced HER2+ breast cancer in terms of overall survival (OS) and disease-free survival (DFS)
An additional finding that corroborates the robustness of the data presented here is that this analysis identified a HR of 0.62 (95% credi bility intervals (CrI):0.52–0.78) for the comparison between chemotherapy alone versus chemotherapy plus one year of trastuzumab, which is very close to the results found in a Cochrane meta-analysis (0.66; 95% CI 0.57–0.77) [33]

Summary

Introduction

Breast cancer is the most common malignancy among women worldwide accounting for 2.4 million new cases and 523,000 deaths yearly [1]. Since the approval of the first HER2-targeted therapy, trastuzumab, in 2001, other anti-HER2-targeted agents have been developed and tested in the metastatic and in the (neo)adjuvant settings, including lapatinib, pertuzumab, neratinib, and TDM1 [9, 10]. Trastuzumab was the cornerstone of the anti-HER2 therapy for the treatment of HER2+ breast cancer until recently, when results of T + P and neratinib after T were approved [11,12,13]. It is not feasible to have adequate pairwise comparative data for all the available treatment options because the number of possible headto-head comparisons directly expands in a quadratic proportion with the availability of effective agents [21]. Several (neo)adjuvant treatments for patients with HER2-positive breast cancer have been compared in different randomized clinical trials. Since it is not feasible to conduct adequate pairwise comparative trials of all these therapeutic options, network meta-analysis offers an opportunity for more detailed inference for evidence-based therapy

Methods

Results

Discussion

Conclusion