Same Story with Different Endings in HER2- Positive Breast Cancer: Why the Benefit of Pertuzumab is Robust in the Metastatic Scenario and Modest in the Adjuvant Setting_ Crimson Publishers

 Same Story with Different Endings in HER2- Positive Breast Cancer: Why the Benefit of Pertuzumab is Robust in the Metastatic Scenario and Modest in the Adjuvant Setting? by Jayesh Sagar* in Surgical Medicine Open Access Journal_ Journal of Surgical Medicine

 

Abstract
The addition of pertuzumab to chemotherapy and trastuzumab yielded an impressive improvement in the outcomes of metastatic HER2-positive breast cancer patients [1]. Intriguingly, the same magnitude of benefit could not be reproduced with pertuzumab in the adjuvant setting, being the reasons for this discrepancy unknown [2,3]. In this manuscript, we discuss clinical and biological differences between metastatic and early-stage HER2-positive breast cancer, and conclude by proposing potential explanations for the distinct magnitudes of benefit of pertuzumab in different disease settings.

Magnitude of Risk Reduction
When evaluating a new treatment in the context of a clinical trial, events occurring in experimental and control arms are compared [4]. Early-stage HER2-positive breast cancer patients treated with adjuvant chemotherapy and trastuzumab had a 87.8% recurrencefree survival rate at 6 years as per the recently updated results of the APHINITY trial [3]. In the metastatic setting, however, the perspective is different: only 20% of patients receiving chemotherapy and trastuzumab remain alive and progression-free at 3 years [1]. Therefore, events are more frequent in the metastatic setting than in early-disease. In other words, there is more room for improvement in metastatic disease, whereas in the adjuvant setting chemotherapy and trastuzumab already yield high Disease-Free Survival (DFS) rates.

Illustrating this hypothesis, the addition of pertuzumab to trastuzumab and chemotherapy in the metastatic setting yields a 32% relative reduction in the risk of progression, which translates into an 8.2% absolute increase in Progression-Free Survival (PFS) at 3 years, whereas in the adjuvant setting pertuzumab yields a 24% relative reduction in the risk of recurrence at 6 years, translating into a modest 2.8% absolute improvement in invasive DFS (iDFS) [1-3]. When considering only node-positive patients (who present a higher risk of recurrence), the benefit of adjuvant pertuzumab becomes more pronounced (28% relative reduction in recurrence risk yielding a 4.5% absolute 6-year iDFS improvement).

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