RT Journal Article
SR Electronic
T1 TBCRC 008: Early Change in <sup>18</sup>F-FDG Uptake on PET Predicts Response to Preoperative Systemic Therapy in Human Epidermal Growth Factor Receptor 2–Negative Primary Operable Breast Cancer
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 31
OP 37
DO 10.2967/jnumed.114.144741
VO 56
IS 1
A1 Connolly, Roisin M.
A1 Leal, Jeffrey P.
A1 Goetz, Matthew P.
A1 Zhang, Zhe
A1 Zhou, Xian C.
A1 Jacobs, Lisa K.
A1 Mhlanga, Joyce
A1 O, Joo H
A1 Carpenter, John
A1 Storniolo, Anna Maria
A1 Watkins, Stanley
A1 Fetting, John H.
A1 Miller, Robert S.
A1 Sideras, Kostandinos
A1 Jeter, Stacie C.
A1 Walsh, Bridget
A1 Powers, Penny
A1 Zorzi, Jane
A1 Boughey, Judy C.
A1 Davidson, Nancy E.
A1 Carey, Lisa A.
A1 Wolff, Antonio C.
A1 Khouri, Nagi
A1 Gabrielson, Edward
A1 Wahl, Richard L.
A1 Stearns, Vered
YR 2015
UL http://jnm.snmjournals.org/content/56/1/31.abstract
AB Epigenetic modifiers, including the histone deacetylase inhibitor vorinostat, may sensitize tumors to chemotherapy and enhance outcomes. We conducted a multicenter randomized phase II neoadjuvant trial of carboplatin and nanoparticle albumin-bound paclitaxel (CP) with vorinostat or placebo in women with stage II/III, human epidermal growth factor receptor 2 (HER2)–negative breast cancer, in which we also examined whether change in maximum standardized uptake values corrected for lean body mass (SULmax) on 18F-FDG PET predicted pathologic complete response (pCR) in breast and axillary lymph nodes. Methods: Participants were randomly assigned to 12 wk of preoperative carboplatin (area under the curve of 2, weekly) and nab-paclitaxel (100 mg/m2 weekly) with vorinostat (400 mg orally daily, days 1–3 of every 7-d period) or placebo. All patients underwent 18F-FDG PET and research biopsy at baseline and on cycle 1 day 15. The primary endpoint was the pCR rate. Secondary objectives included correlation of change in tumor SULmax on 18F-FDG PET by cycle 1 day 15 with pCR and correlation of baseline and change in Ki-67 with pCR. Results: In an intent-to-treat analysis (n = 62), overall pCR was 27.4% (vorinostat, 25.8%; placebo, 29.0%). In a pooled analysis (n = 59), we observed a significant difference in median change in SULmax 15 d after initiating preoperative therapy between those achieving pCR versus not (percentage reduction, 63.0% vs. 32.9%; P = 0.003). Patients with 50% or greater reduction in SULmax were more likely to achieve pCR, which remained statistically significant in multivariable analysis including estrogen receptor status (odds ratio, 5.1; 95% confidence interval, 1.3–22.7; P = 0.023). Differences in baseline and change in Ki-67 were not significantly different between those achieving pCR versus not. Conclusion: Preoperative CP with vorinostat or placebo is associated with similar pCR rates. Early change in SULmax on 18F-FDG PET 15 d after the initiation of preoperative therapy has potential in predicting pCR in patients with HER2-negative breast cancer. Future studies will further test 18F-FDG PET as a potential treatment-selection biomarker.