Correlation of SUV on Early Interim PET with Recurrence-Free Survival and Overall Survival in Primary Operable HER2-Positive Breast Cancer (the TBCRC026 Trial).

Abstract

Predictive biomarkers of response to human epidermal growth factor receptor 2 (HER2)-directed therapy are essential to inform treatment decisions. The TBCRC026 trial reported that early declines in tumor SUVs corrected for lean body mass (SUL_max) on ¹⁸F-FDG PET/CT predicted a pathologic complete response (pCR) to HER2 therapy with neoadjuvant trastuzumab and pertuzumab (HP) without chemotherapy in estrogen receptor (ER)-negative, HER2-positive breast cancer. We hypothesized that ¹⁸F-FDG PET/CT SUL_max parameters would predict recurrence-free survival (RFS) and overall survival (OS). <b>Methods:</b> Patients with stage II/III ER-negative, HER2-positive breast cancer received neoadjuvant HP (<i>n</i> = 88). pCR after HP alone was 22% (18/83), additional nonstudy neoadjuvant therapy was administered in 28% (25/88), and the majority received adjuvant therapy per physician discretion. ¹⁸F-FDG PET/CT was performed at baseline and at cycle 1, day 15 (C1D15). RFS and OS were summarized using the Kaplan-Meier method and compared between subgroups using logrank tests. Associations between ¹⁸F-FDG PET/CT (≥40% decline in SUL_max between baseline and C1D15, or C1D15 SUL_max ≤ 3) and pCR were evaluated using Cox regressions, where likelihood ratio CIs were reported because of the small numbers of events. <b>Results:</b> Median follow-up was 53.7 mo (83/88 evaluable), with 6 deaths and 14 RFS events. Estimated RFS and OS at 3 y was 84% (95% CI, 76%-92%) and 92% (95% CI, 87%-98%), respectively. A C1D15 SUL_max of 3 or less was associated with improved RFS (hazard ratio [HR], 0.36; 95% CI, 0.11-1.05; <i>P</i> = 0.06) and OS (HR, 0.14; 95% CI, 0.01-0.85; <i>P</i> = 0.03), the latter statistically significant. The association of an SUL_max decline of at least 40% (achieved in 59%) with RFS and OS did not reach statistical significance. pCR was associated with improved RFS (HR, 0.25; 95% CI, 0.01-1.24; <i>P</i> = 0.10) but did not reach statistical significance. <b>Conclusion:</b> For the first time, we report a potential association between a C1D15 SUL_max of 3 or less on ¹⁸F-FDG PET/CT and RFS and OS outcomes in patients with ER-negative, HER2-positive breast cancer receiving neoadjuvant HP alone. If confirmed in future studies, this imaging-based biomarker may facilitate early individualization of therapy.