ASCO 2020-CAPECITABINE FOR TNBC WITH RESIDUAL DISEASE AFTER NEOADJUVANT CHEMOTHERAPY

In a phase III trial in patients with early triple-negative breast cancer (TNBC), maintenance therapy with metronomic capecitabine for 1 year following standard treatment significantly improved disease-free survival (DFS), according to data presented during the ASCO20 Virtual Scientific Program (Abstract 507). Metronomic capecitabine was also well tolerated for 1 year, with no unexpected serious adverse events (AEs) observed.

“This is the first phase III clinical trial to apply metronomic chemotherapy in only patients with TNBC and obtain positive results,” said Xi Wang, MD, of Sun Yat-Sen University Cancer Center, China, presenting the final results of the trial, SYSUCC-001, conducted by the South China Breast Cancer Group.

“This is the first phase III clinical trial to apply metronomic chemotherapy in only patients with TNBC and obtain positive results.” – Dr. Xi Wang

Patients with early (stage IB–IIIC) operable TNBC were randomly assigned to receive metronomic capecitabine (650 mg/m² twice daily continuously for 1 year) as maintenance therapy or observation after standard local and systemic treatment for curative intent. The primary endpoint was DFS, and secondary endpoints were distant DFS (DDFS), overall survival (OS), and safety. Of 460 patients assessed for eligibility, 221 patients were randomly assigned to the capecitabine group and 213 to the observation group. Patient characteristics, including tumor size and lymph node status, were well balanced between the two groups.

Dr. Naamit K. Gerber

For the primary endpoint, with a median follow-up of 57 months, 5-year DFS was 83% in patients who received capecitabine maintenance therapy after standard local and systemic treatment of TNBC for curative intent, compared with 73% in patients who were observed after standard treatment (HR 0.63, 95% CI [0.42, 0.96]; p = 0.027).

Five-year DDFS was also significantly better in the capecitabine group than in the observation group (85% vs. 76%, HR 0.63, 95% CI [0.37, 0.90]; p = 0.016). Although 5-year OS was numerically superior in the capecitabine group, the difference between groups was not statistically significant (86% vs. 81%, HR 0.74, 95% CI [0.47, 1.18]; p = 0.203), Dr. Wang noted.

Regarding safety, 91.4% of patients receiving capecitabine completed 1 year of capecitabine therapy as planned, with a median relative dose intensity for capecitabine of 84.7%. The most common capecitabine-related AEs were hand-foot syndrome (45.2%), leukopenia (23.5%), elevated bilirubin (12.7%), abdominal pain/diarrhea (6.8%), and elevated serum transaminases (5.0%). All AEs were grade 1/2, except hand-foot syndrome, with 7.7% of patients in the capecitabine group experiencing grade 3 or greater.

“Unlike the toxicity of standard four-dose treatment, metronomic chemotherapy demonstrates antitumor efficacy by inhibiting angiogenesis and stimulating immune response to reduce tumor metastases; therefore, metronomic chemotherapy might become a valid option for TNBC with a tendency to distant metastases,” Dr. Wang said.

Discussant Naamit K. Gerber, MD, of New York University School of Medicine, noted that capecitabine is approved for use in the metastatic TNBC setting, and subsequent studies have tested its use in the neoadjuvant and adjuvant setting. SYSUCC-001, she said, lends support to the findings of the previous CREATE-X trial and meta-analyses that showed a preferential benefit of capecitabine in TNBC versus ER-positive disease.¹

This trial showed improvement in DFS with continuous daily capecitabine in early-stage TNBC, and the benefit was not restricted to the highest risk patients on subgroup analyses, Dr. Gerber noted. The dosing schedule and toxicity used in this trial appear promising, she said, although SYSUCC-001 was not a head-to-head comparison with intermittent dosing of capecitabine.

As to whether SYSUCC-001 was practice changing, Dr. Gerber noted that most patients with TNBC receive neoadjuvant chemotherapy, and thus a tailored approach based on pathologic response, as used in the CREATE-X trial, would be preferred.

“For the small population of patients who receive adjuvant chemotherapy for higher-stage TNBC and who would have met eligibility criteria for this trial, this approach may be considered, pending publication and peer review,” she said.

— Tim Donald, ELS