PCN344 ADDITION OF PERTUZUMAB TO TRASTUZUMAB-BASED ADJUVANT THERAPY IN HIGH-RISK HER2-POSITIVE EARLY BREAST CANCER: A GRADE-BASED ANALYSIS FROM THE PHASE III APHINITY TRIAL

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Although anti-HER2 (human epidermal growth factor receptor 2) therapies have dramatically improved the prognosis of patients with HER2-positive early breast cancer, some patients relapse despite receiving optimal treatment. In the large phase III APHINITY trial, the addition of 1 year of adjuvant pertuzumab to standard trastuzumab-based adjuvant therapy significantly improved invasive disease-free survival. However, the magnitude of benefit was arguably marginal in the overall patient population. We used the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach on data from APHINITY to build Summary of Findings tables to evaluate the efficacy and safety effects and quality of evidence of predefined clinical outcomes for the addition of pertuzumab to trastuzumab-based adjuvant therapy in patients with high-risk HER2-positive early breast cancer. The addition of pertuzumab was associated with a clinically significant better 3-year, event-free, absolute benefit in disease-free survival, invasive disease-free survival, and distant relapse-free interval in patients with node-positive or hormone receptor-negative disease. There was a more than 20% relative improvement in all relapse-related endpoints, with an absolute benefit of approximately 3 relapse-events fewer/100 patients treated. Although data from APHINITY are not yet mature, there were indications of an absolute benefit in mortality, compared with placebo (standard adjuvant chemotherapy plus trastuzumab), which should be confirmed when the overall survival analysis is conducted. The overall quality of evidence for this GRADE analysis is MODERATE. A good safety profile was confirmed. The application of the GRADE methodology to the APHINITY study provides a strength of evidence in support of the addition of pertuzumab in the adjuvant treatment of HER2-positive early breast cancer patients at higher risk of recurrence because of nodes involvement or hormone receptor-negativity. This data can be useful to guide therapeutic decisions in daily clinical practice.