Abstract P3-14-05: Randomized phase II study of preoperative docetaxel and cyclophosphamide-containing chemotherapy for luminal-type breast cancer

Background: We compared and evaluated three 6-cycle, docetaxel and cyclophosphamide (TC)-containing chemotherapy regimens in a multicenter randomized phase II study. The main aim was to investigate whether anthracyclines are needed or can be omitted, and whether the order of chemotherapy is important, for treating luminal-type breast cancer. Methods: We recruited patients (pts) with ER-positive, HER2-negative breast cancer aged 20–70 years, and histo-pathologically invasive breast cancer (T1c-3, N0-1, M0), T≤7cm. Pts were randomized to 3 groups for the following treatments: 6 cycles of TC; 3 cycles of 5-FU/epirubicin/cyclophosphamide (FEC) followed by 3 cycles of TC (FEC-TC); and 3 cycles of TC followed by 3 cycles of FEC (TC-FEC). TC treatment consisted of administration of docetaxel at 75 mg/m2 and cyclophosphamide at 600 mg/m2 once every 3 weeks. FEC treatment consisted of administration of 5-FU at 500 mg/m2, epirubicin at 100 mg/m2, and cyclophosphamide at 500 mg/m2 once every 3 weeks. We aimed to enroll 65 pts per group based on an expected pCR rate among regimens of adding 10% at a threshold of 9%. The primary endpoint was pathological complete response (pCR) rate. Secondary endpoints were overall response rate (ORR), breast conservation rate and safety. Results: A total of 195 pts (median age, 49.5 years (range, 26–69); median tumor size, 32.8 mm (range, 9–82); 91 pts with N(+) (51%)) were enrolled and randomized as follows: FEC-TC (n = 65), TC-FEC (n = 63), and TC group (n = 67). There were no differences in backgrounds among groups. Both the intention-to-treat population and the safety analysis set included 65, 63 and 65 pts in these groups, respectively. The 6-cycle treatment completion rates were 96.9%, 96.8% and 84.6%, respectively. pCR, defined as yT0/isyN0, was achieved by 9.2% of pts in the FEC-TC group, 8.1% in the TC-FEC group, and 15.9% in the TC group (p = 0.321). A quasi pCR in breast (yT0/is and near pCR) was achieved by 13.9%, 14.5%, and 17.5%, respectively. These responses did not differ among the 3 groups. ORRs, assessed by MRI or CT, were 75.8% (CR: 12.9%), 75% (CR: 5%), and 82.2% (CR: 17.9%) in the FEC-TC, TC-FEC and TC groups, respectively. Breast conservation rates were 50.8%, 45.2%, and 73.0%, respectively.Adverse events of Grade≥3 were observed in 20.0%, 27.0%, and 20.3% of pts in the FEC-TC, TC-FEC, and TC groups, respectively, with no significant differences. Febrile neutropenia was observed in 17.2%, 21.0%, and 11.3%, respectively, but in most cases it was managed sufficiently on an outpatient basis. Of 28, 27 and 23 pts in these groups in whom mastectomy was planned, 9 (32%), 5 (19%), and 10 (44%) were successfully converted to undergo breast-conserving surgery. Of 37, 35 and 40 pts in the FEC-TC, TC-FEC and TC groups in whom breast-conserving surgery was planned, 13 (35%), 12 (34%), and 4 (10%) underwent mastectomy. Conclusion: Six cycles of TC had therapeutic effects and safety equivalent to FEC-TC and TC-FEC. The 3 treatment groups showed similar pCR rates, although the breast conservation rate was significantly higher in the TC group than in the other 2 groups. It may be possible to conduct preoperative chemotherapy for pts with ER-positive breast cancer without using an anthracycline. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-14-05.