Metronomic treatment of vinorelbine with oral capecitabine is tolerable in the randomized Phase 2 study XeNa including patients with HER2 non-amplified metastatic breast cancer

Background: Metronomic treatment is hypothesized to be less toxic and more effective as compared to standard maximal tolerable dosing treatment in metastatic cancer disease. Material and methods: We tested the metronomic treatment principle with vinorelbine in a randomized phase 2 setting combined with standard capecitabine treatment in the XeNa trial with Clinical Trials.gov identifier number: NCT0141771. 120 patients with disseminated HER2 non-amplified breast cancer were included. Randomization was between Arm A: vinorelbine 60 mg/m² day 1 + day 8 in the first cycle followed by 80 mg/m² day 1 + day 8 in the following cycles or Arm B: vinorelbine 50 mg three times a week. Capecitabine 1000 mg/m² twice a day for days 1–14 was administered in both arms. Results: The treatment was generally well-tolerated. The response rate (RR) was 24% (arm A) versus 29% (arm B) (p =.67). The clinical benefit rate (CBR) 46.8% (arm A) versus 51.7% (arm B) (p =.72). We found a median progression-free survival (PFS) of 7.1 months (95% confidence interval [CI] 3.9–10.3) in arm A and 6.3 months (95% CI 4.1–8.5) in arm B (p =.25) whereas median overall survival (OS) was 23.3 months (95% CI 20.2–26.4) in arm A and 22.3 months (95% CI 14.3–30.3) in arm B (p =.76). Conclusions: We confirmed that the combination of vinorelbine and capecitabine was well tolerated. Metronomic treatment can be used with acceptable adverse events (AEs), but we did not find significant difference in the effect compared to the standard treatment.