Abstract
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, HER2-negative breast cancer, in which we also examined whether change in maximum standardized uptake values corrected for lean body mass (SULmax) on FDG-PET predicted pathologic complete response (pCR) in breast and axillary lymph nodes. Methods: Participants were randomly assigned to 12 weeks of preoperative carboplatin (AUC 2 weekly) and nab-paclitaxel (100 mg/m2 weekly) with vorinostat (400 mg oral daily, days 1-3 of every 7-day period) or placebo. All patients underwent FDG-PET and research biopsy pretreatment and on C1D15. The primary endpoint was the pCR rate. Secondary objectives included correlation of change in tumor SULmax on FDG-PET by C1D15 with pCR, and to correlate baseline and change in Ki67 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 days after initiating preoperative therapy between those achieving pCR versus not (percent reduction 63.0% vs. 32.9%; P = 0.003). Patients with ≥50% reduction in SULmax were more likely to achieve pCR, which remained statistically significant in multivariable analysis including estrogen receptor status (OR=5.1; 95% CI=1.3-22.7; P = 0.023). Differences in baseline and change in Ki67 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 FDG-PET 15 days after initiating preoperative therapy has potential in predicting pCR in patients with HER2-negative breast cancer. Future studies will further test FDG-PET as a potential treatment-selection biomarker.
- Copyright © 2014 by the Society of Nuclear Medicine and Molecular Imaging, Inc.