Survival Analysis of the WSG TP-II Trial: Neoadjuvant Trastuzumab and Pertuzumab Plus Endocrine Therapy Versus Chemotherapy in Hormone Receptor-Positive/Human Epidermal Growth Factor Receptor 2-Positive Early Breast Cancer.

Abstract

The WSG TP-II trial (ClinicalTrials.gov identifier: NCT03272477) was designed to compare the impact of 12 weeks of neoadjuvant trastuzumab + pertuzumab combined with endocrine therapy (ET) versus chemotherapy (once per week paclitaxel) on the pathologic complete response (pCR) rate and survival in hormone receptor-positive/human epidermal growth factor receptor 2 (HER2)-positive early breast cancer (eBC). Analysis of the primary end point revealed that the pCR rate in the paclitaxel + trastuzumab + pertuzumab arm was superior compared with that in the ET + trastuzumab + pertuzumab arm (56.4% <i>v</i> 23.7%). Here, we present the final 5-year survival analysis of this multicenter, randomized phase II, open-label trial, with 207 participants randomly assigned 1:1 to the two study arms. All patients received dual HER2 blockade in the adjuvant setting. Further standard chemotherapy was obligatory in all patients with non-pCR, but optional after pCR. After a 5-year follow-up, an overall survival rate of 100% (95% CI, 100.0 to 100.0) in the ET arm versus 97.9% (95% CI, 95.0 to 100.0) in the paclitaxel arm was estimated. The corresponding 5-year event-free survival-ductal carcinoma in situ rates were 92.1% (95% CI, 86.6 to 97.9) versus 94.8% (95% CI, 90.5 to 99.3), and 5-year invasive disease-free survival rates were 97.7% (95% CI, 94.5 to 100.0) versus 79.8% (95% CI, 55.6 to 100.0). Our results show excellent survival outcomes in patients with hormone receptor-positive/HER2-positive eBC who received either a de-escalated chemotherapy or ET in combination with trastuzumab and pertuzumab in the neoadjuvant setting. WSG TP-II confirms the safety and efficacy of a de-escalated and well-tolerated neoadjuvant therapy approach with pCR-guided adjuvant therapy in hormone receptor-positive/HER2-positive eBC.