The effect of standard dose of neo/adjuvant chemotherapy on the benefit from capecitabine maintenance therapy: an exploratory analysis from SYSUCC-001 trial
Authors: Chen Ying , Li Wen-Xia , Wu Jia-Hua , Chen Geng-Hang , Yang Chun-min , Lu Hai , Wang Xi , Wang Shu-Sen , Huang Heng , Cai Li , Zhao Li , Peng Rou-Jun , Lin Ying , Tang Jun , Zeng Jian , Zhang Le-Hong , Ke Yong-Li , Wang Xian-Ming , Liu Xin-Mei , Zhang An-Qin , Xu Fei , Bi Xi-Wen , Huang Jia-Jia , Li Ji-Bin , Pang Dan-Mei , Xue Cong , Shi Yan-Xia , He Zhen-Yu , Lin Huan-Xin , An Xin , Xia Wen , Cao Ye , Guo Ying , Hong Ruo-Xi , Jiang Kui-Kui , Zhong Yong-Yi , Yuan Zhong-Yu , Chen Qian-Jun 
Published: September 2022

Abstract
Aims: The addition of extended capecitabine after standard neo/adjuvant chemotherapy shows controversial results in triple-negative breast cancer (TNBC) patients between SYSUCC-001 trial and CIBOMA trial. Patients presents different responses to diverse regimens, and different dose strengths also affect their prognosis. Hence, we tried to investigate whether the benefit from SYSUCC-001 is effected by the strength of previous adjuvant chemotherapy.
Methods: We reviewed the neo/adjuvant chemotherapy regimens, dose divide by body surface area, etc. of TNBC patients in SYSUCC-001 trial. Their therapeutic dose were classified into consistent and inconsistent with CIBOMA trial. Besides, we stratified patients into the strong regimen arm (A/EC-T and TA/EC) and medium regimen arm (A/EC, TA/E, CMF, FA/EC, FA/EC-T, and TC) according to their specific neo/adjuvant treatment.Subsequently, we compared differences in baseline characteristics between the strong and medium regimen arms, and further investigated the impact of therapeutic regimens and dose on the survival outcome of TNBC patients in SYSUCC-001 trial(the median follow-up is 61months, interquartile range, 44-82months).
Results: A total of 434 TNBC patients were included in this study. Among them, patients who used strong chemotherapy regimen accounted for about 76.74%, and those who used medium regimen accounted for 23.26%. About 32.3% and 52.2% patients received the standard doses of anthracyclines and taxanes separately according to minimum acceptable regimens for chemotherapy in CIBOMA trial. In our analysis we found the dose strength did not affect the DFS in the observe group. However, the standard dose of taxanes improved the DFS in capecitabine group [HR, 2.04 (1.02 - 4.06)]. The interaction analysis showed that the strength of treatment regimenand anthracycline dose did not affect DFS. Whereas, subgroup analysis showed TNBC patients with standard dose of taxanes significantly benefited from capecitabine (P = 0.014). In addition, the standard dose of taxanes could improve DFS.
Conclusions: The strength of neo/adjuvant chemotherapy does not affect the curative effect of capecitabine maintenance chemotherapy. The benefits of the SYSUCC-001 study are mainly from one-year capecitabine administration. Moreover, the standard dose of chemotherapy especially taxanes is a positive factor for the effect of capecitabine treatment. So in some special condition, such as patients can’t endure the side effect of the chemotherapy, we’d better reduce the dose of anthracycline not the taxanes.