Correlation of SUV on Early Interim PET with Recurrence-Free Survival and Overall Survival in Primary Operable HER2-Positive Breast Cancer (the TBCRC026 Trial)
Creators: name: Denbow, Rita
name: Stearns, Vered
name: Liu, Minetta C
name: Carey, Lisa A
name: Connolly, Roisin M
name: Vaklavas, Christos
name: Rimawi, Mothaffar
name: Krop, Ian E
name: Wolff, Antonio C
name: Leal, Jeffrey P
name: Huang, Chiung-Yu
name: Storniolo, Anna Maria
name: Valero, Vicente
name: Specht, Jennifer
name: Winer, Eric P
name: Cimino-Mathews, Ashley
name: Hennessy, Maeve A
name: Wahl, Richard L
name: Solnes, Lilja B
name: Abramson, Vandana G
Publisher: name: Society of Nuclear Medicine
Year: 2023

description: <p>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<sub>max</sub>) on <sup>18</sup>F-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 <sup>18</sup>F-FDG PET/CT SUL<sub>max</sub> parameters would predict recurrence-free survival (RFS) and overall survival (OS). <strong>Methods:</strong> Patients with stage II/III ER-negative, HER2-positive breast cancer received neoadjuvant HP (<em>n</em> = 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. <sup>18</sup>F-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 <sup>18</sup>F-FDG PET/CT (&ge;40% decline in SUL<sub>max</sub> between baseline and C1D15, or C1D15 SUL<sub>max</sub> &le; 3) and pCR were evaluated using Cox regressions, where likelihood ratio CIs were reported because of the small numbers of events. <strong>Results:</strong> Median follow-up was 53.7&thinsp;mo (83/88 evaluable), with 6 deaths and 14 RFS events. Estimated RFS and OS at 3&thinsp;y was 84% (95% CI, 76%-92%) and 92% (95% CI, 87%-98%), respectively. A C1D15 SUL<sub>max</sub> of 3 or less was associated with improved RFS (hazard ratio [HR], 0.36; 95% CI, 0.11-1.05; <em>P</em> = 0.06) and OS (HR, 0.14; 95% CI, 0.01-0.85; <em>P</em> = 0.03), the latter statistically significant. The association of an SUL<sub>max</sub> 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; <em>P</em> = 0.10) but did not reach statistical significance. <strong>Conclusion:</strong> For the first time, we report a potential association between a C1D15 SUL<sub>max</sub> of 3 or less on <sup>18</sup>F-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.</p>