Randomized phase II study of ramucirumab or icrucumab in combination with capecitabine in patients with previously treated locally advanced or metastatic breast cancer

Background. Icrucumab (ICR) and ramucirumab (RAM) bind vascular endothelial growth factor (VEGF) receptors 1 and 2 (VEGFR-1 and-2), respectively. This open-label, randomized phase II study evaluated their efficacy and safety in combination with capecitabine (CAP) in patients with previously treated unresectable, locally advanced ormetastatic breast cancer. Methods. Patients were randomly assigned (1:1:1) to receive CAP (1,000 mg/m² orally twice daily, days 1-14) alone or in combination with RAM (10 mg/kg intravenously [IV], days 1 and 8) (RAM1CAP) or ICR (12 mg/kg IV, days 1 and 8) (ICR1 CAP) every 21 days. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), tumor response, safety, and pharmacokinetics. Results. Of 153 patients randomized, 150 received treatment. Median PFS (95% confidence interval) was 22.1 (12.1-36.1) weeks on RAM1CAP, 7.3 (6.3-13.0) weeks on ICR1CAP, and 19.0 (12.1-24.3) weeks on CAP (hazard ratios [HRs]: 0.691, p5.1315, RAM1CAP versus CAP; 1.480, p5.0851, ICR1 CAP versus CAP). Median OS was 67.4 weeks on RAM1CAP, 62.1 weeks on ICR1CAP, and 71.6 weeks on CAP (HRs: 1.833, p5.0283, RAM1CAP versus CAP; 1.468, p5.1550, ICR1 CAP versus CAP). There was no statistically significant difference in PFS or OS between either combination arm and CAP. Treatment-related adverse events more frequent (by ≥ 10%) on RAM1CAP than on CAP were constipation, decreased appetite, headache, epistaxis, and hypertension. Those more frequent (by ≥ 10%) on ICR1CAP than CAP were anemia, increased lacrimation, periorbital edema, nausea, vomiting, peripheral edema, facial edema, dehydration, and dyspnea. Conclusion. Combining RAM or ICR with CAP did not improve PFS in the targeted study population.