Abstract P1-14-15: A randomized phase lll trial of neoadjuvant sequential chemotherapy with 4 cycles of adriamycin plus cyclophosphamide followed by 4 cycles of docetaxel (AC4-D4) versus shorter 3 cycles of FEC followed by 3 cycles of docetaxel (FEC3-D3) in node-positive breast cancer (Neo-Shorter): First report of efficacy & toxicity profile
Authors: Kim JE , Ahn J-H , Jung KH , Lee HJ , Gong G-Y , Lee E-M , Ha EJ , Son B-H , Ahn S-H , Ahn SD , Kim H-H , Shin HJ , Kim S-B 
Published: May 2016

Background: The addition of a taxane to anthracycline-based chemotherapy provided an improved outcome in neoadjuant setting. Two neoadjuvant chemotherapy with 4 cycles of AC followed by 4 cycles of docetaxel (AC4-D4) and 3 cycles of FEC followed by 3 cycles of docetaxel (FEC3-D3) are widely used. Short duration of chemotherapy, 6 cycles rather than 8 cycles might be an attractive approach.

Methods: This is a randomized, single-center, prospective, parallel group, comparative phase III trial (NCT02001506). Patients (pts) with breast cancer of clinically stage II or III, or sized  1.5 cm with histologically proven lymph-node involvement were included. Pts were stratified according to hormone receptor and HER2 expression status and randomized to AC4-D4 and 3 cycles of FEC3-D3 treatment. The primary endpoint was pathological complete response, defined as the absence of invasive disease in the breast and axillary lymph nodes, analyzed by intention to treat.

Results: At the time of submission, a total of 207 pts were enrolled; 1 pt failed screening; 25 pts dropped out (5 pts in AC4-D4 arm and 2 pts in FEC3-D3 arm discontinue treatment due to progressive disease); 39 pts are still receiving neoadjuvant chemotherapy; 142 pts, who received surgery, were included for this analysis. In AC4-D4 arm, among 64 pts, 57 pts achieved clinical response (6 complete response [CR] and 51 partial response [PR]) and among them 9 pts achieved pathologic complete response [pCR]. In FEC3-D3 arm, among 78 pts, 66 pts achieved clinical response (7 CR and 59 PR) and among them 11 pts achieved pCR. Addition of docetaxel increased clinical response in both arms. The most common adverse event was febrile neutropenia. Without prophylactic G-CSF, grade ≥3 febrile neutropenia (FN) occurred 23/661 cycles (3.5%) in AC4-D4 arm and 23/552 cycles (4.2%) in FEC3-D3 arm, respectively. Grade 3 and 4 toxicities other than FN were reported at expected levels in both groups. Sixty-one severe adverse events were reported; 33 (including 23 FN) in AC4-D4 arm and 28 (including 23 FN) in FEC3-D3 arm.

Conclusion: Compared to AC4-D4, shorter duration of FEC3-D3 neoadjuvant chemotherapy showed similar efficacy of pCR rate of 14.0% (versus 14.1% in AC4-D4 arm). The most common and important adverse event was febrile neutropenia in both arms. Updated study findings will be provided.

Citation Format: Kim JE, Ahn J-H, Jung KH, Lee HJ, Gong G-Y, Lee E-M, Ha EJ, Son B-H, Ahn S-H, Ahn SD, Kim H-H, Shin HJ, Kim S-B. A randomized phase lll trial of neoadjuvant sequential chemotherapy with 4 cycles of adriamycin plus cyclophosphamide followed by 4 cycles of docetaxel (AC4-D4) versus shorter 3 cycles of FEC followed by 3 cycles of docetaxel (FEC3-D3) in node-positive breast cancer (Neo-Shorter): First report of efficacy & toxicity profile. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P1-14-15.