according to results of a phase 3 trial.
Patients who received metronomic capecitabine maintenance had significantly higher rates of 5-year DFS and distant DFS, but not OS, when compared with patients who did not receive capecitabine, reported Xi Wang, PhD, of Sun Yat-sen University Cancer Center in Guangzhou, China, whoas part of the American Society of Clinical Oncology virtual scientific program.
“TNBC has the worst outcomes among all subtypes of breast cancer,” Dr. Wang said. “Effective strategies to reduce risk of relapse are a critical clinical need.”
He went on to describe capecitabine as a “potential ideal drug for metronomic administration,” particularly among patients with high risk of distant metastasis.
With that in mind, Dr. Wang and colleagues tested metronomic capecitabine maintenance in the phase 3 SYSUCC-001 trial. The trial included 434 patients with invasive ductal carcinoma. They had undergone standard therapy, which included surgery, neoadjuvant/adjuvant chemotherapy, and radiation therapy.
Patients were randomized to receive capecitabine at 650 mg/m2 twice daily for 1 year (n = 221) or undergo observation (n = 213). The primary endpoint was DFS, while secondary endpoints included safety, distant DFS, and OS.
According to Dr. Wang, the two patient groups were “well balanced,” with similar baseline characteristics. Most patients underwent adjuvant chemotherapy (93%), had histological grade 3 tumors (71%-74%), had a Ki-67 index of at least 30% (73%-80%), had negative lymph node status (61%-62%), had a tumor size of 2.1-5 cm (55%-58%), and/or pathologic stage II disease (54%-55%).
Survival and safety
At a median follow-up of 56.5 months, the median 5-year DFS rate was 83% in the capecitabine group, compared with 73% in the observation group (P = .027). Similarly, capecitabine use correlated with a significantly better rate of distant DFS (85% vs. 76%; P = .016).
Although the capecitabine group demonstrated a slight trend toward improved OS at 5 years, this finding was not statistically significant (86% vs. 81%; P = .203).
Capecitabine was generally well tolerated, with 91% of patients completing 1 year of therapy, and 75% completing therapy at the full dose.
Almost half of patients in the capecitabine group experienced hand-foot syndrome (45%), and one in four developed leukopenia (24%). Less common adverse events included hyperbilirubinemia (13%), gastrointestinal pain (7%), and elevated serum transaminases (5%). No unexpected serious adverse events occurred.
Effects on practice
, of the Icahn School of Medicine at Mount Sinai in New York, suggested these findings may lead to broader use of capecitabine among patients with TNBC.
“[This is a] very exciting study showing an impressive disease-free survival benefit in the adjuvant setting for capecitabine in patients with early stage TNBC,” Dr. Tiersten said. “Presently, we only have positive data for capecitabine in patients with residual disease after neoadjuvant therapy, but this current study now suggests that this benefit could extend to all comers.”
Dr. Tiersten advised that the medical community stay tuned, since longer-term data may provide a clearer picture of survival benefit.
“It will be interesting to see if there is an impact on overall survival with further follow-up,” she said.
According to invited discussant, of New York University, the results support previous findings from the CREATE-X trial, along with meta-analyses that have shown a “preferential benefit” of capecitabine when used to treat TNBC, compared with estrogen receptor–positive disease.
Still, Dr. Gerber noted that, for most patients, the findings from the SYSUCC-001 trial are unlikely to influence clinical decision-making since most patients with TNBC receive neoadjuvant chemotherapy followed by treatment based on pathologic response. However, she also suggested that, after peer review, the findings could influence treatment for a select few.
“For the small population of patients who receive adjuvant chemotherapy for higher-stage TNBC and who would have met eligibility criteria, this approach may be considered,” Dr. Gerber said.
The study was funded by the Sun Yat-sen University Clinical Research 5010 Program. The investigators disclosed no conflicts of interest. Dr. Gerber reported a relationship with OncLive. Dr. Tiersten reported no relevant disclosures.
SOURCE: Wang X et al. ASCO 2020, .