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Everolimus Improves Progression-Free Survival in Patients with Previously Treated Metastatic RCC

Motzer RJ, Escudier B, Oudard S, et al.
Published: Tuesday, Mar 22, 2011
 Attendees browse the poster sessionsA subgroup analysis of a randomized trial showed that patients with previously treated metastatic renal cell carcinoma (RCC) had significant improvement in progression-free survival (PFS) when they received everolimus.

The inhibitor of mammalian target of rapamycin (mTOR) slowed progression two- to threefold compared with placebo in patients who had received up to 2 prior vascular endothelial growth factor (VEGF) inhibitors. Patients treated with 1 VEGF inhibitor had a 43% longer PFS interval. The difference between treatment groups was similar to that observed in the primary analysis and achieved statistical significance irrespective of the number of prior anti-VEGF agents, as reported at the ASCO Genitourinary Cancers Symposium.

“Everolimus provides clinical benefit over placebo in all patient subgroups, including those previously treated with 1 or 2 VEGF receptor tyrosine kinase inhibitors [TKIs],” said Robert A. Figlin, MD, an oncologist at City of Hope in Duarte, California. “Regardless of prior response to VEGF-TKI therapy, everolimus was associated with clinical benefit in prolonging progression-free survival compared with placebo.”

The findings came from a new analysis of the first RECORD-1 (Renal Cell Cancer Treatment with Oral RAD 001 Given Daily) trial. The study involved 416 patients with metastatic RCC that had progressed during treatment with sunitinib, sorafenib, or both agents. Patients were randomized 2:1 to everolimus or placebo plus best supportive care and were followed until progression. The primary endpoint was PFS.

RECORD-1 ended prematurely after a planned interim analysis showed significant improvement in PFS in the everolimus arm of the trial.* The results showed a median PFS of 4.9 months with everolimus versus 1.9 months for placebo by central review and a difference of 5.5 versus 1.9 months by investigator assessment.

The RECORD-1 patient population was stratified a priori according to the number of prior VEGF-TKI therapies received and by Memorial Sloan-Kettering Cancer Center risk category. Figlin reported findings from the prespecified analysis of outcome by prior therapies.

RECORD-1 included 217 patients previously treated with 1 anti-VEGF agent and 99 patients treated with 2 agents in the class. Baseline characteristics were comparable between patients randomly allocated to everolimus or placebo. The subgroup analysis showed that patients previously treated with 1 VEGF-TKI had a median PFS of 5.42 months with everolimus and 1.87 months with placebo (P <.001). Patients who had received both sunitinib and sorafenib had a median PFS of 3.78 months with everolimus and 1.87 months with placebo (P <.001).

Figlin noted that 2 patients with a treatment history of 1 anti-VEGF agent had partial responses, as did 1 patient who had received 2 prior VEGF-targeted therapies. Additionally, 62% to 63% of each group had stable disease, resulting in a clinical benefit rate of 63% to 64% in both groups.

“Regardless of response on prior VEGF-TKI therapy, the percentage of patients with stable disease who received everolimus was about 2 times higher than those who received placebo,” said Figlin. “The difference is similar to what was observed in the overall RECORD-1 patient population.”

The safety analysis yielded results similar to those of the primary data review. The most common adverse events in the everolimus and placebo groups, respectively, were stomatitis (44% versus 8%), infection (37% vs 18%), asthenia (33% vs 23%), fatigue (31% vs 27%), diarrhea (30% vs 7%), cough (30% vs 16%), and pneumonitis (14% vs 0%).

Laboratory abnormalities were more common in the everolimus group, including decreased hemoglobin (92% vs 79%); increased cholesterol (77% vs 35%), triglycerides (73% vs 34%), and glucose (57% vs 25%); and decreased lymphocyte count (51% vs 28%).

“Results of this preplanned analysis showed that the hazard ratios for the subgroup comparisons were consistent with those calculated for the overall RECORD-1 population,” said Figlin. “The median progression-free survival of the 2 placebo groups was similar also.”

“Everolimus was tolerated, with no differences in adverse events in patients treated with 1 versus 2 prior VEGF-TKIs,” he added.


Motzer RJ, Escudier B, Oudard S, et al. For the RECORD-1 Study Group. Phase 3 trial of everolimus for metastatic renal cell carcinoma: final results and analysis of prognostic factors. Cancer. 2010;116:4256-4265.


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