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

Int J Cancer. 2021 Apr 1;148(7):1685-1694. doi: 10.1002/ijc.33349. Epub 2020 Oct 26.

Abstract

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 and 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 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) >25 vs ≤25 kg/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 >25 kg/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% and disease control rate was 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 >25 kg/m2 benefited most.

Trial registration: ClinicalTrials.gov NCT01266837.

Keywords: 6-month PFS rate; everolimus; phase IV; renal cell carcinoma; second-line.

Publication types

  • Clinical Trial, Phase IV
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Anemia / complications
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / toxicity
  • Body Mass Index
  • Carcinoma, Renal Cell / complications
  • Carcinoma, Renal Cell / drug therapy*
  • Carcinoma, Renal Cell / pathology
  • Everolimus / administration & dosage*
  • Everolimus / adverse effects
  • Everolimus / toxicity
  • Fatigue / complications
  • Female
  • Gastrointestinal Hemorrhage / complications
  • Gastrointestinal Hemorrhage / mortality
  • Humans
  • Kaplan-Meier Estimate
  • Kidney Neoplasms / complications
  • Kidney Neoplasms / drug therapy*
  • Kidney Neoplasms / pathology
  • Male
  • Middle Aged
  • Progression-Free Survival
  • Proportional Hazards Models
  • Prospective Studies
  • Receptors, Vascular Endothelial Growth Factor / antagonists & inhibitors*
  • Stomatitis / complications
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Everolimus
  • Receptors, Vascular Endothelial Growth Factor

Associated data

  • ClinicalTrials.gov/NCT01266837