Temsirolimus Improves Survival in Renal Cell Carcinoma Patients

November 1, 2007

Temsirolimus (Torisel) improves overall survival in patients with clear-cell renal cell carcinoma (RCC) and other histologies, including papillary RCC, according to a study presented at the 43rd annual meeting of the American Society of Clinical Oncology (ASCO), held in Chicago. The exploratory analyses, reported in a poster presentation by Janice Dutcher, MD, and an international team of colleagues, suggest that temsirolimus benefits patients regardless of age or tumor histology, and may benefit those in both poor- and intermediate-risk groups.

Temsirolimus (Torisel) improves overall survival in patients with clear-cell renal cell carcinoma (RCC) and other histologies, including papillary RCC, according to a study presented at the 43rd annual meeting of the American Society of Clinical Oncology (ASCO), held in Chicago. The exploratory analyses, reported in a poster presentation by Janice Dutcher, MD, and an international team of colleagues, suggest that temsirolimus benefits patients regardless of age or tumor histology, and may benefit those in both poor- and intermediate-risk groups.

Study Design

The investigators performed planned and post hoc analyses using data from the phase III global Advanced Renal Cell Carcinoma (ARCC) trial to assess survival in patients treated with temsirolimus based on tumor histology (clear-cell vs other), age (< 65 years vs ≥ 65 years), and prognostic risk groups (Memorial Sloan-Kettering Cancer Center [MSKCC]) intermediate- vs poor-risk groups. The ARCC investigation was a pivotal open-label, randomized clinical trial comparing temsirolimus or a combination of temsirolimus plus interferon-alpha to interferon-alpha alone as first-line therapy in 626 patients with advanced RCC and poor prognostic features.

Patients received interferon-alpha, 3 million units (MU) subcutaneously three times weekly, escalating to 18 MU; temsirolimus, in a 25-mg intravenous infusion weekly; or temsirolimus via 15-mg infusion plus interferon-alpha, 6 MU. Kaplan-Meier analysis and a Cox proportional hazards model were used to analyze overall survival (OS) and progression-free survival (PFS) for patient subsets.

Survival Results

For patients with clear-cell tumors, median OS and PFS were longer for temsirolimus vs interferon-alpha (OS: 10.6 vs 8.2 months; PFS: 5.5 vs 3.8 months), with hazard ratios (HR) of 0.85 and 0.84, respectively. For patients with other tumor histologies, median survival findings also were longer for temsirolimus vs interferon-alpha (OS: 11.6 vs 4.3 months; PFS: 7.0 vs 1.8 months), with HR of 0.55 and 0.36, respectively. The investigators speculated that the overall survival benefit seen in other histologies may be greater than that in clear-cell RCC because cytokines are less active in non–clear-cell RCC.

Among patients less than 65 years old, median OS and PFS were longer for temsirolimus than for interferon-alpha (12.0 vs 6.9 months and 5.9 vs 3.1 months; HR = 0.67 and 0.69). There was no difference in OS or PFS for patients aged 65 and older, but temsirolimus had a better side-effect profile than interferon-alpha.

Quality-Adjusted Survival

In a related ASCO poster discussion by Shreekant Parasuraman, phd, of Wyeth Research, Collegeville, Pa, overall survival time of patients with advanced RCC enrolled in the pivotal study was categorized into three distinct health states:

• Toxicity, defined as time spent with any severe or life-threatening treatment-related toxicity before disease progression

• Relapse, defined as the period following disease progression, ending with death or censoring

• Time without symptoms of progression or toxicity.

Patients were asked to complete quality-of-life questionnaires at several points: at weeks 12 and 32 of the study, when they experienced a serious adverse event, and upon relapse, progression of disease, or withdrawal from the study. Their answers were used to determine quality-adjusted time without symptoms or toxicity, a predefined endpoint.

The analysis showed that patients treated with temsirolimus had a 38% greater time without symptoms and toxicity than those receiving interferon-alpha alone (6.5 vs 4.7 months, respectively; P = .00048). When results of the questionnaires were incorporated into the analysis, patients treated with temsirolimus had 23% greater quality-adjusted survival time than those receiving interferon-alpha alone, a significant 1.3-month increase (7.0 vs 5.7 months, P = .0015).

Concluding Remarks

"The results of these analyses expand our understanding of temsirolimus in patients with advanced kidney cancer," said Dr. Dutcher, who is associate director for clinical affairs, Our Lady of Mercy Medical Center, Bronx, NY, and professor of medicine, New York Medical College, Valhalla, NY. "The data also improve our knowledge of patients' perception of their health during this time on therapy."

The US Food and Drug Administration approved temsirolimus for the treatment of advanced RCC just prior to this year's ASCO meeting.