The investigational once-daily oral mammalian target of rapamycin (mTOR) inhibitor RAD001 (with the proposed brand name Afinitor), formerly known as RAD001, significantly prolongs disease-free survival in patients with metastatic renal cell cancer who have stopped responding to targeted therapy, investigators reported here at the 33rd Annual Congress of the European Society of Medical Oncology (ESMO).

Bernard Escudier, MD, with the Institut Gustave Roussy in Villejuif, France, presented results in 410 patients who had been randomized in a 2:1 design to treatment with RAD001 10 mg/d plus best supportive care or placebo plus best supportive care.

Participants in the trial were stratified according to Memorial Sloan-Kettering Cancer Center (MSKCC) risk criteria and prior anti-cancer therapy.

All patients had metastatic renal cell carcinoma and had failed treatment with the currently available multitargeted receptor tyrosine kinase inhibitors sorafenib or sunitinib or both agents.

The phase III trial, known as REnal Cell Cancer Treatment with Oral RAD001, was halted early to allow patients assigned to placebo to switch to the active drug because it had proven so effective.

Progression-free survival (PFS) determined by central radiology review, the study’s primary endpoint, showed a statistically significant improvement with RAD001 treatment compared to placebo. Specifically, the median PFS with RAD001 was 4.90 months versus 1.96 months for placebo, which translated into a 67% reduction in the risk of progression.

Investigator assessment of PFS corroborated the findings of the central radiology review.

Interim results also demonstrated that RAD001 significantly extended the time without tumor growth from 1.9 to four months.

While grade ¾ adverse drug reactions occurred in 1% or more of patients were more common in the RAD001 cohort, most were temporary or considered easily manageable.

Overall, the results confirm that RAD001 is the first and only agent with established clinical benefit for the treatment of patients with renal cell cancer after failure of VEGFr-TKI therapy, Dr. Escudier said.

RAD001 was recently granted a priority review by the U.S Food and Drug Administration as treatment for advanced renal cell carcinoma. A marketing authorization application has also been filed with the European Medicines Agency (EMEA).

A spokesperson for Novartis, which developed RAD001, said that plans are underway to test the drug in combination with bevacizumab as first-line therapy in renal cell carcinoma and also to examine whether sunitinib or RAD001 should be used as first-line or second-line therapy. The drug is also being explored for potential use in neuroendocrine tumors, lymphoma, other cancers, and tuberous sclerosis as solo therapy or in tandem with existing cancer therapies.

Written by Jill Stein
Jill Stein is a Paris-based freelance medical writer.