Adding capecitabine to adjuvant chemo improves 15-year OS in early breast cancer

Adding capecitabine to adjuvant chemotherapy containing docetaxel, epirubicin and cyclophosphamide significantly improves 15-year overall survival (OS) in patients with early breast cancer, results of the phase III FinXX trial (Finland Capecitabine Trial) have shown.

In the open-label multicentre trial, 1,500 patients with axillary node-positive or high-risk node-negative early breast cancer (median age, 53 years; median tumour diameter, 22 mm; oestrogen receptor [ER]–positive cancer, 76.4 percent; HER2-positive cancer, 18.9 percent), accrued between 27 January 2004 and 29 May 2007, were randomized to receive adjuvant treatment with the TX-CEX regimen consisting of three cycles of docetaxel (T) plus capecitabine (X) followed by three cycles of cyclophosphamide, epirubicin and capecitabine (CEX) (n=753), or the T-CEF regimen consisting of three cycles of T followed by three cycles of cyclophosphamide, epirubicin and fluorouracil (CEF) (n=747). Adjuvant trastuzumab was allowed for patients with HER2-positive disease after May 2005, and was administered to 13 percent vs 11 percent of patients in the TX-CEX vs T-CEF group. [J Clin Oncol 2022;doi:10.1200/JCO.21.02054]

After a median follow-up of 15.3 years in the TX-CEX group and 15.4 years in the T-CEF group, a significant improvement in OS was found in the TX-CEX vs T-CEF group (hazard ratio [HR], 0.81; 95 percent confidence interval [CI], 0.66 to 0.99; p=0.037). The 15-year OS rate was 77.6 percent in the TX-CEX group vs 73.3 percent in the T-CEF group.

Subgroup analyses showed OS benefit with TX-CEX vs T-CEF in patients with triple-negative breast cancer (HR, 0.59; 95 percent CI, 0.36 to 0.97), ER-negative breast cancer (HR, 0.67; 95 percent CI, 0.46 to 0.99), and HER2-negative breast cancer (HR, 0.79; 95 percent CI, 0.64 to 0.99).

Earlier 5-year and 10-year follow-up analyses of FinXX did not show significant improvement in OS with TX-CEX vs T-CEF, although the HRs (0.73 [95 percent CI, 0.52 to 1.04; p=0.080] and 0.84 [95 percent CI, 0.66 to 1.07; p =0.15], respectively) did not differ markedly from the HR in the current analysis. [J Clin Oncol 2012;30:11-18; JAMA Oncol 2017;3:793-800] “This suggests that the study … did not have sufficient power for assessing OS in the previous analyses with shorter follow-up times, leading to a premature conclusion that addition of capecitabine does not prolong OS,” the researchers noted.

“[Results of the current analysis showed that] addition of capecitabine to a chemotherapy regimen that included docetaxel, cyclophosphamide and epirubicin improved OS in a patient population with early breast cancer during a median follow-up of 15 years,” they concluded. “These results suggest that adjuvant capecitabine-containing chemotherapy could be considered an option for some patients with early breast cancer.”

Of note, the OS benefit in the TX-CEX group was achieved despite a lower Q3W docetaxel dose compared with the T-CEF group (60 mg/m² vs 80 mg/m²).

“The capecitabine dosing selected [900 mg/m² twice daily on days 1–15 of the 3-week cycle] was moderate and in the same order of magnitude as was used in other trials evaluating adjuvant or neoadjuvant capecitabine,” the researchers explained. [J Natl Cancer Inst 2008;100:542-551; Cancer 2015;121:3639-3648; JAMA Oncol 2017;3:793-800; N Engl J Med 2017;376:2147-2159; Lancet Oncol 2017;18:929-945; J Clin Oncol 2019;37:2338-2348; J Clin Oncol 2020;38:203-213; J Clin Oncol 2020;38:1774-1784]

“With this dosing, the safety of TX-CEX was considered acceptable,” they noted. [Lancet Oncol 2009;10:1145-1151; J Clin Oncol 2012;30:11-18]