Adding ramucirumab to docetaxel prolonged progression-free survival in patients with locally advanced or metastatic urothelial carcinoma in the second-line treatment setting, a study published in the Journal of Clinical Oncology has shown.1
For the phase 2 study, researchers sought to evaluate the efficacy and safety of docetaxel monotherapy or docetaxel in combination with the vascular endothelial growth factor receptor 2 (VEGFR2) antibody ramucirumab or the VEGFR1 antibody icrucumab following progression on or after platinum-based therapy in patients with locally advanced or metastatic urothelial carcinoma.
Researchers enrolled 140 patients and randomly assigned them 1:1:1 to receive 75 mg/m2 IV on day 1 of each 21-day cycle (arm A), docetaxel 75 mg/m2 IV plus ramucirumab 10 mg/kg IV on day 1 of each 21-day cycle (arm B), or docetaxel 75 mg/m2 IV on day 1 plus icrucumab 12 mg/kg IV on days 1 and 8 of each 21-day cycle (arm C). Treatment was continued until disease progression or unacceptable toxicity.
Results showed that median progression-free survival was 5.4 months (95% CI, 3.1 – 6.9) in arm B compared with 2.8 months (95% CI, 1.9 – 3.6) in arm A (HR, 0.389; 95% CI, 0.235 – 0.643; P = .0002), suggesting a significant benefit with ramucirumab.
In contrast, there was no significant difference in median progression-free survival in arm C compared with arm A (1.6 months; 95% CI, 1.4 – 2.9; HR, 0.863; 95% CI, 0.550 – 1.357; P = .5053).
In terms of safety, the most frequently observed grade 3 or worse adverse events were neutropenia (36%, 33%, and 39%), fatigue (13%, 30%, and 20%), febrile neutropenia (13%, 17%, and 6.1%), and anemia (6.7%, 13%, and 14%, respectively).
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The findings suggested that the combination of docetaxel and ramucirumab for the second-line treatment of patients with locally advanced or metastatic urothelial carcinoma warrants further investigation in a phase 3 trial.
The same combination is approved by the U.S. Food and Drug Administration (FDA) for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) with disease progression on or after platinum-based therapy.
- Petrylak DP, Tagawa ST, Kohli M, et al. Docetaxel as monotherapy or combined with ramucirumab or icrucumab in second-line treatment for locally advanced or metastatic urothelial carcinoma: an open-label, three-arm, randomized controlled phase II trial [published online ahead of print February 29, 2016]. J Clin Oncol. doi: 10.1200/JCO.2015.65.0218.