Everolimus after failure of one prior VEGF-targeted therapy in metastatic renal cell carcinoma: Final results of the MARC-2 trial.

MARC-2, a prospective, multicenter phase IV trial, aimed to investigate clinical outcomes in patients with metastatic renal cell carcinoma (mRCC) treated with everolimus after failure of one initial vascular endothelial growth factor receptor tyrosine kinase inhibitor (VEGFR-TKI) therapy and to identify subgroups benefiting most, based on clinical characteristics and biomarkers. Patients with clear cell mRCC failing one initial VEGFR-TKI received everolimus until progression or unacceptable toxicity. Primary endpoint was 6-month progression-free survival rate (6moPFS). Secondary endpoints were overall response rate (ORR), PFS, overall survival (OS) and safety. Between 2011-2015, 63 patients were enrolled. Median age was 65.4 years (range 43.3-81.1). 6moPFS was 39.3% (95%-confidence interval [CI] 27.0-51.3) overall, 54.4% (95%-CI 35.2-70.1) vs 23.7% (95%-CI 10.5-39.9) for patients aged ≥65 years vs <65 years, and 51.4% (95%-CI 34.7-65.7) vs 18.2% (95%-CI 5.7-36.3) for patients with body mass index (BMI) >25kg/m2 vs ≤25kg/m2 . A Cox proportional hazards model confirmed a longer PFS for patients aged ≥65 years (Hazard Ratio [HR] 0.46, 95% CI 0.26-0.80) and a longer OS for patients with BMI >25kg/m2 (HR 0.36, 95% CI 0.18-0.71). Median PFS and median OS were 3.8 months (95%-CI 3.2-6.2) and 16.8 months (95%-CI 14.3-24.3). ORR was 7.9%, disease control rate 60.3%. No new safety signals emerged. Most common adverse events were stomatitis (31.7%), fatigue (31.7%) and anemia (30.2%). One patient died from treatment-related upper gastrointestinal hemorrhage. Everolimus remains a safe and effective treatment option for mRCC patients after one prior VEGFR-TKI therapy. Patients aged ≥65 years and patients with BMI >25kg/m2 benefited most.