Phase II Trial Supports Use of First-Line Sunitinib vs Everolimus in Sequential Therapy in Metastatic Renal Cell Carcinoma


Key Points

  • Progression-free survival with first-line everolimus was not noninferior to that with sunitinib.
  • Median progression-free survival was longer with sequential sunitinib then everolimus compared with everolimus then sunitinib.

As reported by Motzer et al in the Journal of Clinical Oncology, the randomized phase II RECORD-3 trial showed that first-line use of everolimus did not achieve noninferiority in progression-free survival vs sunitinib (Sutent) in patients with metastatic renal cell carcinoma receiving sequential therapy.

Study Details

In this open-label multicenter crossover trial, 471 patients with metastatic renal cell carcinoma were randomly assigned to receive first-line everolimus at 10 mg/d continually (n = 238) or sunitinib at 50 mg/d for 4 weeks on followed by 2 weeks off treatment (n = 233), with each group receiving the other drug after disease progression.

The primary endpoint was progression-free survival noninferiority of first-line everolimus vs first-line sunitinib. The criteria for noninferiority were a hazard ratio (HR) < 1.1 for everolimus vs sunitinib and an upper bound of the one-sided 90% confidence interval (CI) < 1.27.

Noninferiority Not Achieved

The primary endpoint was not met, with median progression-free survival being 7.9 months for first-line everolimus vs 10.7 months for first-line sunitinib (HR = 1.4, 95% CI = 1.2–1.8, upper bound of one-sided 90% CI = 1.64).

Outcomes of Sequential Therapy

Among patients who discontinued first-line therapy, 45% of everolimus patients crossed over to second-line sunitinib and 43% of sunitinib patients crossed over to second-line everolimus. The median combined progression-free survival was 21.1 months for sequential everolimus then sunitinib vs 25.8 months for sequential sunitinib then everolimus (HR = 1.3, 95% CI = 0.9–1.7). Median overall survival was 22.4 vs 32.0 months (HR = 1.2, 95% CI = 0.9–1.6).

Common adverse events of any grade during first-line everolimus and sunitinib were stomatitis (53% and 57%), fatigue (45% and 51%), and diarrhea (38% and 57%). Grade 3 and 4 noninfectious pneumonitis occurred in 1% and < 1% of patients during first-line everolimus and in no patients during second-line everolimus.

The investigators concluded, “Everolimus did not demonstrate noninferiority compared with sunitinib as a first-line therapy. The trial results support the standard treatment paradigm of first-line sunitinib followed by everolimus at progression.”

Robert J. Motzer, MD, of Memorial Sloan Kettering Cancer Center, is the corresponding author for the Journal of Clinical Oncology article.

The RECORD-3 trial was sponsored by Novartis Pharmaceuticals. For full disclosures fo the study authors, visit

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.