Response-Guided Neoadjuvant Approach Offers Benefits

A response-guided approach to neoadjuvant chemotherapy may boost disease-free survival (DFS) in patients with breast cancer, particularly those with hormone receptor–positive (HR+) tumors, according to a study published in the Journal of Clinical Oncology.

The findings are based on data from the GeparTrio study, a prospective phase III trial conducted by the German Breast Group (GBG), based in Neu-Isenburg, Germany.

The trial enrolled 2,012 patients diagnosed with stage II or III breast cancer. Prior to surgery, all patients received two cycles of docetaxel, doxorubicin, and cyclophosphamide (TAC). Their responses were then measured, and they were stratified as early responders (who achieved tumor reduction of 50% or more) and nonresponders.

The 1,390 early responders were randomized to receive an additional four (standard arm) or six (response-guided arm) cycles of TAC before surgery. The 622 nonresponders were randomized to four cycles of TAC (standard arm) or non–cross-resistant treatment (response-guided arm) of vinorelbine and capecitabine (NX) before surgery.

At a median follow-up of 62 months, DFS was 22% longer in the early responders who received total of eight TAC cycles compared to the standard six, and their overall survival (OS) showed only a trend toward improvement, with an increase of 24%.

DFS improved by 41% in early nonresponders who were assigned to the response-guided arm rather than the standard arm. However, no OS benefit was observed relative to patients in the standard arm during the follow-up period.

Pathologic complete response (pCR), defined as no residual invasive and no noninvasive disease in any excised breast or regional node tissue, which was the primary endpoint of the GeparTrio trial, showed no significant benefit from a response-guided approach. “After analysis of the primary endpoint, pCR, we did not expect to see positive results in DFS and OS,” says lead author and GBG chairman Gunter von Minckwitz, MD, PhD, a professor of gynecology at the University of Frankfurt in Germany.

A subgroup analysis revealed that survival benefits were restricted to patients with HR+ disease, which von Minckwitz says explains the unexpected results. “This is the subgroup of patients where pCR seems to have less prognostic impact,” he says. “In hormone receptor–negative patients, where pCR is a strong prognostic marker, treatment results based on pCR and outcomes are in concordance.”

While studying DFS or OS requires years of follow-up, von Minckwitz argues that they remain important endpoints, particularly in trials involving HR+ disease.

“Our analysis shows a real advantage of taking a response-guided neoadjuvant approach,” says von Minckwitz. “It also shows that in HR+ disease, where chemotherapy is considered to have lower absolute effects, chemotherapy approaches have to be used in a more sophisticated manner.”

Von Minckwitz says another prospective study is required to replicate these findings, and that the GBG is exploring the possibility of conducting such subsequent trials.