TY - JOUR
T1 - Correlation of SUV on Early Interim PET with Recurrence-Free Survival and Overall Survival in Primary Operable HER2-Positive Breast Cancer (the TBCRC026 Trial)
AU - Hennessy, Maeve A.
AU - Leal, Jeffrey P.
AU - Huang, Chiung Yu
AU - Solnes, Lilja B.
AU - Denbow, Rita
AU - Abramson, Vandana G.
AU - Carey, Lisa A.
AU - Liu, Minetta C.
AU - Rimawi, Mothaffar
AU - Specht, Jennifer
AU - Storniolo, Anna Maria
AU - Valero, Vicente
AU - Vaklavas, Christos
AU - Winer, Eric P.
AU - Krop, Ian E.
AU - Wolff, Antonio C.
AU - Cimino-Mathews, Ashley
AU - Wahl, Richard L.
AU - Stearns, Vered
AU - Connolly, Roisin M.
N1 - Publisher Copyright:
© 2023 Society of Nuclear Medicine Inc.. All rights reserved.
PY - 2023/11/1
Y1 - 2023/11/1
N2 - 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 (SULmax) 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 SULmax parameters would predict recurrence-free survival (RFS) and overall survival (OS). Methods: Patients with stage II/III ER-negative, HER2-positive breast cancer received neoadjuvant HP (n 5 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 SULmax between baseline and C1D15, or C1D15 SULmax # 3) and pCR were evaluated using Cox regressions, where likelihood ratio CIs were reported because of the small numbers of events. Results: 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 SULmax of 3 or less was associated with improved RFS (hazard ratio [HR], 0.36; 95% CI, 0.11–1.05; P 5 0.06) and OS (HR, 0.14; 95% CI, 0.01–0.85; P 5 0.03), the latter statistically significant. The association of an SULmax 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; P 5 0.10) but did not reach statistical significance. Conclusion: For the first time, we report a potential association between a C1D15 SULmax 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.
AB - 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 (SULmax) 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 SULmax parameters would predict recurrence-free survival (RFS) and overall survival (OS). Methods: Patients with stage II/III ER-negative, HER2-positive breast cancer received neoadjuvant HP (n 5 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 SULmax between baseline and C1D15, or C1D15 SULmax # 3) and pCR were evaluated using Cox regressions, where likelihood ratio CIs were reported because of the small numbers of events. Results: 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 SULmax of 3 or less was associated with improved RFS (hazard ratio [HR], 0.36; 95% CI, 0.11–1.05; P 5 0.06) and OS (HR, 0.14; 95% CI, 0.01–0.85; P 5 0.03), the latter statistically significant. The association of an SULmax 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; P 5 0.10) but did not reach statistical significance. Conclusion: For the first time, we report a potential association between a C1D15 SULmax 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.
KW - biomarkers
KW - breast cancer
KW - FDG PET/CT
KW - HER2-positive
KW - neoadjuvant
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U2 - 10.2967/jnumed.123.265853
DO - 10.2967/jnumed.123.265853
M3 - Article
C2 - 37652539
AN - SCOPUS:85175867181
SN - 0161-5505
VL - 64
SP - 1690
EP - 1696
JO - Journal of Nuclear Medicine
JF - Journal of Nuclear Medicine
IS - 11
ER -