204P Clinical Features Predictive of Never-Progressive Disease to First-Line Anti-Her2 Therapy: Real-world Data from the ESME National Cohort

First-line (1L) anti-HER2 therapy has dramatically improved survival for patients (pts) with HER2+ metastatic breast cancer (MBC). We investigated clinicopathologic predictors of never progressive disease (PD) in the multicenter, real-world ESME-MBC cohort (NCT03275311). We selected women with HER2+ MBC diagnosed between 2008 and 2021 and treated with 1L anti-HER2-based therapy who had not experienced PD within 36 months (mo) of MBC diagnosis and with ≥60 mo of follow-up (fu). We used a multivariable logistic regression model with backward selection and bootstrap cross-validation to identify clinicopathologic characteristics of pts who never had PD at the last fu (still in 1L). Among 4, 697 pts with HER2+ MBC, 1, 083 had not experienced progression at 36 mo, of whom 318 were excluded due to fu <60mo, yielding a final study population of 765 pts. Of them, 523 (68.3%) never developed PD during fu (median fu of 97.9 mo (95%CI 94.8-101.9). Median progression-free survival (PFS) was 106.4mo (95%CI 92.8-130.8), and 60mo PFS was 68.4% (IC95% 65.1-71.7). Hormone receptor negative (HR-) status, use of 1L chemotherapy (CT) + dual HER2 inhibition, and absence of visceral metastases at diagnosis were independently associated with never PD at last fu (Odds Ratio (OR) 1.74 (1.23 – 2.48), 1.51 (1.07 – 2.14), 0.51 (0.24 – 1.12), respectively Table). The model's predictive performance had an AUC of 0.64.Table: 204PMultivariable predictors of never PDNOR [95%CI]PTumor gradeI/II39310.004III2811.48 [1.05 ; 2.09]Undeterminate482.90 [1.37 ; 6.91]Age at MBC<55 yrs36310.022≥55 yrs3590.68 [0.49 ; 0.95]First-line regimenCT + H28510.045CT+HP3681.51 [1.07 ; 2.14]Other690.98 [0.56 ; 1.73]HRHR+45310.002HR-2691.74 [1.23 ; 2.48]Metastases site at diagnosisNon-visceral33110.037Visceral non CNS3580.68 [0.48 ; 0.95]CNS330.51 [0.24 ; 1.12]H: Trastuzumab, P: Pertuzumab Open table in a new tab H: Trastuzumab, P: Pertuzumab In this large cohort, pts who had at least 3 years of disease control under 1L anti-HER2 therapy had 68.4% odds of remaining progression-free 2 years later. Negative hormone receptor status was the main driver of this long-term control. This may support de-escalation strategies in HER2+ patients with long-standing response to therapy. However, effective biomarkers to predict never PD beyond clinicopathologic features are warranted.