Response-Guided Neoadjuvant Chemotherapy for Breast Cancer

William J. Gradishar, MD

Survival was significantly improved for patients with hormone receptor–positive tumors.

Multiple large clinical trials have shown that early clinical response to preoperative chemotherapy correlates with pathologic response at the time of surgery and overall survival. Now, German Breast Group researchers have conducted a prospective, phase III trial (GeparTrio) to evaluate response-guided neoadjuvant chemotherapy in 2072 patients with histologic confirmation of breast cancer. Patients also had ≥1 of the following risk factors: age <36, clinical tumor size >5 cm, estrogen receptor (ER) and progesterone receptor (PR) negativity, clinical axillary node involvement, or undifferentiated tumor grade. Patients with features of locally advanced breast cancer, including inflammatory breast cancer, were allowed.

The 1390 responders to an initial 2 cycles of TAC (docetaxel, doxorubicin, and cyclophosphamide) therapy were considered chemosensitive and were randomly assigned to either 4 or 6 more TAC cycles. The 633 nonresponders to initial therapy were considered resistant to TAC and were randomly assigned to either 4 more TAC cycles or 4 cycles of the non–cross-resistant regimen of vinorelbine and capecitabine (NX).

After a median follow-up of 62 months, results were as follows:

• Disease-free survival (DFS) was longer in early responders receiving 8 versus 6 TAC cycles (hazard ratio, 0.78; P=0.026).
• DFS was longer in early nonresponders receiving TAC plus NX versus 6 TAC cycles (HR, 0.59; P=0.001).
• Exploratory analysis showed that DFS was longer after response-guided chemotherapy (8 TAC cycles or TAC plus NX) versus 6 TAC cycles (HR, 0.71; P=0.003), as was overall survival (HR, 0.79; P=0.048).
• DFS was longer after response-guided chemotherapy in all hormone receptor–positive tumors (luminal A HR, 0.55, luminal B [HER2-negative] HR, 0.40, and luminal B [HER2-positive] HR, 0.56), but not in hormone receptor–negative tumors (HER2-positive [nonluminal] or triple-negative); pathologic complete response (pCR) did not predict these survival effects.
• pCR predicted improved DFS in triple-negative (HR, 6.67), HER2-positive–nonlumina (HR, 5.24), and luminal B HER2-negative tumors (HR, 3.74).

Citation(s):

von Minckwitz G et al. Response-guided neoadjuvant chemotherapy for breast cancer. J Clin Oncol 2013 Sep 3; [e-pub ahead of print].

Telli ML et al. Insight or confusion: Survival after response-guided neoadjuvant chemotherapy in breast cancer. J Clin Oncol 2013 Sep 3; [e-pub ahead of print].