Abstract PS13-07: Neoadjuvant adriamycin plus cyclophosphamide followed by docetaxel (AC4-D4) vs 5-fluorouracil, epirubicin plus cyclophosphamide followed by docetaxel (FEC3-D3) in stage II or III operable breast cancer : Randomized phase III neo-shorter trial (NCT02001506)
Authors: Hwang Inhwan , Kim Jeong Eun , Jeong Jae Ho , Ahn Jin-Hee , Jung Kyung Hae , Son Byung Ho , Ahn Sei-Hyun , Lee Hee Jin , Gong Gyungyub , Kim Sung-Bae 
Published: February 2021

Background: Two neoadjuvant anthracycline and taxane containing chemotherapy regimens have been widely used. The objective of the study was shorter duration of 6 cycles of FEC3-D3 is comparable to 8 cycles of AC4-D4 Method: Enrolled patients (pts) were diagnosed clinically stage II or III breast cancer between November 2012 and December 2015 at Asan Medical Center, Seoul, Korea. Pts were stratified according to hormone receptor and HER2 expression status and randomized 1:1 to AC4-D4 and FEC3-D3 arm. The primary endpoint was pathologic complete response (pCR) and the secondary end points were 3 year disease-free survival (3Y DFS) and toxicities.Result: Among 252 pts enrolled, 1pt ineligible for screening; 10 pts discontinued treatment due to progressive disease (7 pts in AC4-D4 arm and 3 pts in FEC3-D3), 17 pts dropped out due to withdrawal of written consent and 2 pts unable to complete study. Two hundred twenty two pts receiving surgery were included for this analysis. Baseline characteristics are well balanced between two arms- median age (47 vs 48), % of TNBC (24% vs 26%) in AC4-D4 (N=126) vs FEC3-D3 arm (N=125) respectively. Baseline median Ki-67 labeling index was 50% (range, 10%-90%). By ITT analysis, pCR was achieved in 18/126 (14.3%) pts of AC4-D4 arm and 15/125 (12.0%) pts in FEC3-D3 arm, respectively (p=0.17). According to per protocol, in AC4-D4 arm, 95/103 pts achieved clinical response (6 complete response [CR] and 89 partial response [PR]) and among them 18 pts (17.5%) achieved pCR. In FEC3-D3 arm, 97/119 pts achieved clinical response (4 CR and 93 PR) and among them 15 pts (12.6%) achieved pCR. With a median follow up of 64.1 months, 3Y DFS (77.0% in AC4-D4 vs. 74.9% in FEC3-D3) was comparable between two arms (p=0.79). The most common adverse event (AE) was Grade 3/4 neutropenia. 44/126 (34.9%) pts in AC4-D4 arm vs 39/125 (31.2%) pts in FEC3-D3 arm. The most common Grade 3/4 non-hematologic AE was hyperglycemia (3.2%). Dose modification was done in 37/126 (29.4%) pts in AC4-D4 arm and 25/125 (20.0%) pts in FEC3-D3 arm, respectively (p=0.09). Multivariate analyses showed that ≥50% of baseline Ki-67 labeling index [hazard ratio (HR) 2.1 (95% confidence interval (CI),1.20-3.72; p=0.009)], ≥40% of pre-treatment Ki-67 labeling index reduction after neoadjuvant chemotherapy(NACT) [HR 2.1 (95% CI,1.20-3.66; p=0.01)], and ≥4 lymph node metastases at surgery [HR 2.2 (95% CI,1.24-3.80; p=0.07)] were independent predictive factors for 3Y DFS. Of note, in patients with non-pCR, ≥ 40% reduction of Ki-67 after NACT was associated with better 3Y DFS in luminal type [HR 2.9 (95% CI,1.51-5.65; p=0.001)]. Conclusion: Both NACT AC4-D4 and FEC3-D3 showed comparable outcomes in terms of pCR, 3 year DFS and toxicities. ≥50% of baseline Ki-67 labeling index and ≥40% reduction of Ki-67 labeling index after NACT were independent for 3Y DFS. Shorter neo-adjuvant FEC3-D3 could be an alternative to AC4-D4 in stage II or III operable breast cancer.Keywards: Neoadjuvant, AC followed by docetaxel, FEC followed by docetaxel, operable breast cancer

Citation Format: Inhwan Hwang, Jeong Eun Kim, Jae Ho Jeong, Jin-Hee Ahn, Kyung Hae Jung, Byung Ho Son, Sei-Hyun Ahn, Hee Jin Lee, Gyungyub Gong, Sung-Bae Kim. Neoadjuvant adriamycin plus cyclophosphamide followed by docetaxel (AC4-D4) vs 5-fluorouracil, epirubicin plus cyclophosphamide followed by docetaxel (FEC3-D3) in stage II or III operable breast cancer : Randomized phase III neo-shorter trial (NCT02001506) [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS13-07.