Preliminary data from an interim analysis of an ongoing phase III clinical trial of investigational temsirolimus (CCI-779) for the treatment of advanced renal cell carcinoma showed that single-agent therapy with temsirolimus significantly increased overall survival as a first-line treatment of patients with advanced disease and poor-risk features compared to interferon-alpha, a treatment for advanced renal cell carcinoma. In the trial, patients who were treated with temsirolimus alone experienced a 3.6-month, or 49%, increase in median overall survival time compared with patients treated with interferon-alpha alone (10.9 vs 7.3 months, P = .0069). These data were presented during a late-breaking plenary session at the 42nd annual meeting of the American Society of Clinical Oncology (ASCO) in Atlanta.

Temsirolimus is a specific inhibitor of mTOR (mammalian target of rapamycin), a signaling protein that regulates cell growth and angiogenesis.

"Advanced renal cell carcinoma is a particularly difficult form of cancer to treat, and despite recent advances, patients still have few treatment options," says Gary Hudes, MD, director, genitourinary malignancies program, Fox Chase Cancer Center, Philadelphia. "The ability to improve survival for these patients with advanced renal cell carcinoma and poor-risk features by 3½ months is quite an achievement, and shows that mTOR inhibition may be a viable approach in this disease area."

Interim Analysis

This open-label, randomized, phase III trial compared temsirolimus alone or a combination of temsirolimus plus interferon-alpha to interferon-alpha alone as first-line therapy. Participants included 626 patients with advanced renal cell carcinoma and poor-risk features who had received no prior systemic therapy. The primary endpoint of the study was overall survival.

In this interim analysis, the median survival of patients who were treated with investigational temsirolimus alone was 49% longer compared with patients who were treated with interferon-alpha alone. The median overall survival time among patients in the combination group was 15% longer than in the interferon-alpha group, though this result was not statistically significant.

The most significant adverse events reported in arm 1 (interferon-alpha alone), arm 2 (temsirolimus alone), and arm 3 (temsirolimus in combination with interferon-alpha) included asthenia (27%, 12%, and 30%, respectively), anemia (24%, 21%, and 39%), and dyspnea (8%, 9%, and 11%). Among the 626 patients enrolled in the study, 442 deaths had occurred by the time of this interim analysis. Patients remain on treatment and continue to be followed for survival in this ongoing study.

In August 2004, the US Food and Drug Administration (FDA) granted fast-track designation for temsirolimus for first-line treatment for patients with advanced renal cell carcinoma and poor-risk features. In December 2004, the FDA granted orphan drug designation to investigational temsirolimus for the treatment of advanced renal cell carcinoma.