Response-guided neoadjuvant chemotherapy may improve disease-free and overall survival in patients with early breast cancer, particularly in those patients with hormone receptor–positive tumors, findings from an exploratory analysis of data from the phase III GeparTrio trial suggest.
"Our exploratory analyses of this prospective trial strongly suggest that the various breast cancer phenotypes require different chemotherapy approaches and show that even patients with luminal tumors can derive greater benefit from response-guided chemotherapy," Dr. Gunter von Minckwitz of the German Breast Group, Neu-Isenburg, and his colleagues reported, noting that the findings must be tested prospectively but can be used to guide the design of future trials.
After treating 2,072 patients with two cycles of docetaxel, doxorubicin, and cyclophosphamide (TAC), the researchers randomized 1,390 early responders to receive either four or six additional TAC cycles, and randomized 622 early nonresponders either to four additional TAC cycles or to non-cross-resistant treatment with vinorelbine and capecitabine (TAC-NX) before surgery. TAC cycles included 75 mg/m2 of docetaxel, 50 mg/m2 of doxorubicin, and 500 mg/m2 of cyclophosphamide on day 1 every 3 weeks. NX included 25 mg/m2 of vinorelbine on days 1 and 8 plus 1,000 mg/m2 of capecitabine given orally twice daily on days 1-14 every 3 weeks. Sixty patients did not continue in the study after the initial TAC cycles.
Disease-free survival was better in the 686 early responders who received a total of eight TAC cycles, compared with the 704 patients who received six TAC cycles (hazard ratio, 0.78), and in 301 early nonresponders who received TAC-NX, compared with 321 early nonresponders who received six TAC cycles (HR, 0.59), the investigators reported online Sept. 3 in the Journal of Clinical Oncology.
An exploratory analysis demonstrated that both disease-free survival and overall survival were longer following either eight TAC cycles or TAC-NX, as compared with conventional chemotherapy with six TAC cycles (HRs, 0.71 and 0.79, respectively), the investigators reported (J. Clin. Oncol. 2013 Sept. 3 [doi: 10.1200/JCO.2012.45.0940]).
"Treatment effects on overall survival were less pronounced. Responders receiving TAC x 8 showed only a trend toward longer overall survival compared with those receiving TAC x 6 (hazard ratio, 0.76), whereas nonresponders receiving TAC-NX showed no improvement in overall survival compared with those receiving TAC x 6 (hazard ratio, 0.85). Response-guided chemotherapy provided significant but marginal overall survival benefit over conventional chemotherapy (hazard ratio, 0.79)," they said.
Of note, the effects of response-guided therapy on disease-free survival were apparent in all hormone receptor–positive tumors but not in hormone receptor–negative tumors, they noted (HRs for luminal A, luminal B HER2-negative, and luminal B HER2-positive tumors were 0.55, 0.40, and 0.56, respectively; HRs for nonluminal HER2-positive and triple-negative tumors were 1.01 and 0.87, respectively).
Pathological complete response (pCR) did not predict long-term outcomes; a comparison of pCR rates based on treatment strategy showed that "survival in patients with hormone receptor–positive tumors did not depend on pCR but was improved by response-guided therapy, whereas survival in patients with hormone receptor–negative tumors did depend on pCR but was not improved by response-guided therapy," they said. pCR predicted improved disease-free survival in triple-negative, nonluminal HER2-positive, and luminal B HER2-negative tumors (HRs, 6.67, 5.24, and 3.74, respectively), they reported.
Patients included in the study had unilateral or bilateral primary breast cancer confirmed by core biopsy, and had at least one additional risk factor, including age under 36, clinical tumor size more than 5 cm, estrogen receptor and progesterone receptor negativity, clinical axillary node involvement, or undifferentiated tumor grade.
The findings from the GeparTrio study demonstrate the advantage of neoadjuvant versus adjuvant chemotherapy. Response-guided treatment can only be conducted when the tumor is available for the monitoring of response, the investigators noted.
This study was supported by Amgen, Chugai, Roche, and Sanofi-Aventis. Dr. von Minckwitz and multiple coauthors reported serving as a consultant or advisor for, owning stock in, and/or receiving honoraria or research funding from Amgen, Roche, Sanofi-Aventis, and other companies.