228P The impact of initial tumor response to docetaxel, trastuzumab, and pertuzumab on survival outcomes of patients with HER2+ metastatic breast cancer: An exploratory analysis of the CLEOPATRA trial

The combination of docetaxel (D) with trastuzumab and pertuzumab (T+P) remains the standard first-line in metastatic HER2-positive breast cancer (BC), based on the results of the CLEOPATRA trial. However, all patients (pts) do not benefit equally from this therapy. We explored the association between survival outcomes and initial tumoral response to D+T+P. We performed an exploratory analysis of CLEOPATRA (NCT00567190) using data extracted from the Vivli database (ID:00007856). The primary objective was to assess the overall survival (OS) of pts treated with D+T+P according to their response at the first tumor assessment at 9 weeks. Secondary objective was progression-free survival (PFS). Response was classified as complete (CR), partial (PR), or stable (SD), according to RECIST1.0 based on central review as per original trial. Pts without first tumor assessment were excluded. We performed a log-rank test to compare Kaplan-Meier curves, and uni- and multivariate analysis. We applied Extended Cox Regression Model to consider a possible guarantee-time bias. In D+T+P arm, 362/402 pts were included: 12.7% (46/62) with CR, 67.1% (243/362) with PR, and 20.2% (73/362) with SD. In CR group, 47.8% of pts had de novo disease (61.3% in PR, 43.8% in SD, Fisher’s exact test p=0.015), 69.6% had visceral disease (83.3% in PR, 67.1% in SD, p=0.005), 60.9% were hormone receptor (HR) negative (51.9% in PR, 49.3% in SD, p=NS). After a median (m) follow-up of 4.1 years, pts in CR group had a significantly longer PFS compared to PR or SD (log-rank p<0.001), and a longer OS compared to PR or SD (mOS not reached (NR), 57.3 mo (interquartile (IQR) 32.1-NR) and 43.4 mo (IQR 22-103.5) in the CR, PR, and SD group, respectively, p=0.002). In multivariate analysis, a high body mass index was associated with better OS in SD group (HR=0.93 95%; confidence interval (CI) (0.88-0.99) p=0.023), ECOG ≥1 with worse OS in PR group (HR=1.66 95% CI (1.17-2.36) p=0.005). The outcome benefit of CR was equal in HR- and HR+ tumors, p=NS. Obtaining an early radiological CR with D+T+P confers significantly longer OS and PFS, whereas no difference is observed once compared with PR and SD.