The prognosis and risk factors for capecitabine maintenance treatment in metastatic breast cancer: a retrospective comparative cohort study

Background: Maintenance treatment following efficient chemotherapy can improve the treatment outcomes of patients with metastatic breast cancer (MBC). However, there are no studies for identifying the prognostic factors for patients who could benefit from capecitabine maintenance. Therefore, this study aimed to investigate the prognosis and risk factors of capecitabine maintenance therapy and analysed the circulating tumour DNA (ctDNA) markers that may be related to the treatment response. Methods: This study recruited 482 consecutive patients with MBC who achieved clinical benefit from capecitabine-based chemotherapy from 2011 to 2019. A total of 256 patients received subsequent capecitabine maintenance therapy. The baseline clinical factors included age at diagnosis, menopause, neoadjuvant therapy, estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) status and subtypes, prior treatment lines, and prior capecitabine-based treatment response. Treatment outcome (progression-free survival, PFS) was assessed by imaging tools according to RSCIST 1.1 standard during the first two treatment cycles and every 3 weeks thereafter. Univariate and multivariate Cox proportional hazards models were used to analyse the association between capecitabine maintenance treatment and prognosis. Results: The median PFS of patients receiving capecitabine maintenance treatment was 21.7 months [95% confidence interval (CI): 15.1-36.3 months]. Capecitabine maintenance showed similar effects as endocrine maintenance or anti-HER2 therapy in hormone receptor (HR)-positive or HER2-positive patients, with adjusted HR of 1.17 (95% CI: 0.81-1.71, P=0.40). In patients with triple-negative breast cancer (TNBC), capecitabine maintenance showed a marginal benefit in PFS. Compared to late-line (>= 2) capecitabine maintenance, first-line capecitabine maintenance significantly prolonged median PFS. Compared to other HR/ HER2 subtypes, patients with HR-positive and HER2-positive subtypes significantly benefited from capecitabine maintenance treatment. Analysis of ctDNA revealed that among patients receiving capecitabine maintenance, TP53 aberrations were concentrated in patients with short PFS. Conclusions: Capecitabine maintenance treatment is associated with longer PFS in patients with MBC, especially those receiving first-line capecitabine-based chemotherapy and those with HR positivity/HER2 positivity. TP53 aberrations may be responsible for the poor response to capecitabine maintenance treatment.