Replacing a cyclophosphamide-based regimen with oral capecitabine does not sacrifice efficacy in adjuvant therapy for early breast cancer, and improves quality of life (QOL), according to a new study. Increasing the dose density of the anthracycline portion of therapy, however, did not add any benefit to therapy.
Results of the study were published in Lancet Oncology.
“Current outcomes for patients with early breast cancer reflect advances in diagnosis and therapy, including the standardization of adjuvant systemic therapy,” wrote study authors led by David Cameron, MD, of Cancer Research UK Edinburgh Center. Studies have shown, though, that epirubicin followed by cyclophosphamide, methotrexate, and fluorouracil (CMF) carries significant toxicity.
The phase III TACT2 trial used a 2 × 2 factorial design to test whether accelerating the epirubicin portion of therapy could improve efficacy without increasing toxicity, and whether CMF could be replaced without losing efficacy. It included a total of 4,391 patients, randomized to either a standard or accelerated epirubicin schedule, followed by four 4-week cycles of either CMF or four 3-week cycles of capecitabine. All patients had node-positive or high-risk node-negative disease, and had undergone complete excision.
After a median follow-up of 85.6 months, no difference was seen between the accelerated and standard epirubicin schedules with regard to time to tumor recurrence (TTR; defined as first invasive relapse or breast cancer death). A total of 377 of 2,221 standard epirubicin patients (17%) had a TTR event, compared with 347 of 2,170 accelerated epirubicin patients (16%), for a hazard ratio (HR) for TTR of 0.94 (95% CI, 0.81–1.09; P = 0.42). Adjustment for factors known to influence prognosis did not change the result significantly.
Replacing CMF with capecitabine did not sacrifice efficacy, as there was also no difference in TTR between those two groups. The HR for TTR was 0.98 (95% CI, 0.85–1.14; P = .00092 for non-inferiority). Overall survival also did not differ between the groups; at 3 years, the overall survival was 95.2% with CMF and 94.7% with capecitabine. At 5 years, these rates were 90.2% and 90.1%, respectively.
A QOL and toxicity substudy included 2,121 patients. After epirubicin treatment, QOL as measured by the EORTC QLQ-C30 was significantly worse in those who had received the accelerated schedule, but that difference did not persist at 12 and 24 months. QOL was also worse following CMF treatment than capecitabine therapy, and this did persist at 12 and 24 months; a longitudinal analysis confirmed the poorer QOL in CMF patients (P < .0001).
“There is no one universal standard regimen for adjuvant chemotherapy in breast cancer,” the authors wrote. “In TACT2 we have shown that increasing the dose density of the anthracycline component of chemotherapy did not improve disease outcomes or QOL. However, we did confirm that capecitabine may be used in place of CMF with reduced overall toxicity.”