Data Presented at ASCO Showed TORISEL Significantly Increased Quality-Adjusted Survival for Patients with Advanced Renal Cell Carcinoma
dditional Data Examined Overall Survival in Patients with Advanced RCC Regardless of Tumor Cell Type
Collegeville, Pa.– Wyeth Pharmaceuticals, a division of Wyeth (NYSE:WYE), today presented two analyses of the phase 3 clinical trial of TORISEL™ (temsirolimus) for the treatment of advanced renal cell carcinoma (RCC) at a poster discussion session at the 43rd American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, Ill. Investigators concluded that TORISEL improves overall survival of patients with advanced RCC with both clear-cell and other tumor cell types, and that patients with advanced RCC who were treated with TORISEL had significantly greater quality-adjusted survival − a measure that incorporates patient feedback regarding their time without symptoms and side effects − than those treated with interferon-alpha.
Renal cell carcinoma accounts for approximately 85 percent of kidney cancers. The American Cancer Society estimates that 51,190 new cases of kidney cancer will be diagnosed this year, and more than 40 percent of patients will be diagnosed initially with advanced disease.
The two abstracts are analyses of data from the pivotal trial of TORISEL, an open-label, randomized, phase 3 clinical trial comparing TORISEL or a combination of TORISEL plus interferon-alpha to interferon-alpha alone as first-line therapy in 626 patients with advanced RCC and poor prognostic features.
“The results of these analyses expand our understanding of temsirolimus in patients with advanced kidney cancer,” says Janice Dutcher, M.D., Associate Director for Clinical Affairs, Our Lady of Mercy Medical Center, Bronx, N.Y., and Professor of Medicine, New York Medical College, Valhalla, N.Y. “The data also improve our knowledge of patients’ perception of their health during this time on therapy.”
About Abstract 5049: Comparison of Quality-Adjusted Survival Time in Patients With Advanced Renal Cell Carcinoma Receiving First-Line Treatment With Temsirolimus (TEMSR) or Interferon-α (IFN) or the Combination of IFN+TEMSR
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 pre-defined endpoint.
The analysis showed that patients treated with TORISEL had 38 percent greater time without symptoms and toxicity than those receiving interferon-alpha alone (6.5 months vs. 4.7 months, respectively; P=.00048). When results of the questionnaires were incorporated into the analysis, patients treated with TORISEL had 23 percent greater quality-adjusted survival time than those receiving interferon-alpha alone, a significant 1.3-month increase (7.0 months vs. 5.7 months, P=.0015).
About Abstract 5033: Correlation of Survival With Tumor Histology, Age and Prognostic-Risk Group for Previously Untreated Patients With Advanced Renal Cell Carcinoma Receiving Temsirolimus or Interferon Alpha
Investigators conducted planned and post-hoc analyses to assess the influence of tumor cell type (clear-cell renal cell carcinoma vs. other renal cell carcinomas), age (younger than 65 years vs. 65 years and older) and prognostic-risk group (intermediate risk vs. poor risk) on survival in patients treated with TORISEL or interferon-alpha.
TORISEL increased overall survival and progression-free survival regardless of tumor cell type compared to interferon-alpha. Median overall survival in patients with clear-cell tumors, the most common form of RCC, was 10.6 months among patients treated with TORISEL versus 8.2 months for interferon-alpha, and median progression-free survival was 5.5 months versus 3.8 months, respectively, as determined by independent assessment. For patients with other tumor cell types, differences in median overall survival and progression-free survival were even greater. Median overall survival was more than twice as long in patients treated with TORISEL compared with interferon-alpha (11.6 months vs. 4.3 months), and median progression-free survival was nearly four times longer (7.0 months vs. 1.8 months, respectively).
Among patients younger than 65 years, both overall survival and progression-free survival were longer in those treated with TORISEL (12.0 months vs. 6.9 months and 5.9 months vs. 3.1 months, respectively) compared with interferon-alpha. There was no statistical difference between the two arms in overall survival or progression-free survival for patients aged 65 and older.
Researchers also examined survival endpoints based on patients’ prognostic risk. About three quarters of patients with advanced RCC enrolled in the TORISEL arm or interferon-alpha arm of the study were classified as having poor prognostic features. Of these patients, those treated with TORISEL had significantly longer overall survival (10.2 months vs. 6.0 months, P=.0272) and progression-free survival (5.1 months vs. 2.3 months, P=.0440). The study did not include enough patients with intermediate prognostic factors to allow for meaningful assessment of differences in survival.
TORISEL is an mTOR inhibitor indicated for the treatment of advanced RCC. In in vitro studies using cancer cells, mTOR inhibition blocked the translation of genes that regulate the cell cycle. mTOR inhibition also resulted in reduced levels of certain cell growth factors involved in the development of new blood vessels, such as vascular endothelial growth factor.
Important Safety Information
Hypersensitivity reactions manifested by symptoms, including, but not limited to anaphylaxis, dyspnea, flushing, and chest pain have been observed with Torisel.
The use of Torisel is likely to result in increases in serum glucose. This may result in the need for an increase in the dose of, or initiation of, insulin and/or oral hypoglycemic agent therapy. The use of Torisel is likely to result in increases in serum triglycerides and cholesterol. This may require initiation, or increase in the dose, of lipid-lowering agents.
The use of Torisel may result in immunosuppression. Patients should be carefully observed for the occurrence of infections, including opportunistic infections.
Cases of interstitial lung disease, some resulting in death, have occurred with Torisel. Some patients were asymptomatic and others presented with symptoms and required discontinuation of Torisel treatment and/or corticosteroids, and/or antibiotics.
Bowel perforation may occur. Evaluate fever, abdominal pain, bloody stools and/or acute abdomen promptly.
Renal failure, sometimes fatal, has occurred. Monitor renal function at baseline and while on Torisel.
Due to abnormal wound healing, use Torisel with caution in the perioperative period.
Patients with central nervous system tumors (primary CNS tumor or metastases) and/or receiving anticoagulation therapy may be at an increased risk of developing intracerebral bleeding (including fatal outcomes) while receiving Torisel.
Live vaccinations and close contact with those who received live vaccines should be avoided.
Women of childbearing potential should be advised of the potential hazard to the fetus and to avoid becoming pregnant.
The most common adverse reactions observed with Torisel are: rash, asthenia, mucositis, nausea, edema, and anorexia. The most common laboratory abnormalities are anemia, hyperglycemia, hyperlipemia, hypertriglyceridemia, elevated alkaline phosphatase, elevated serum creatinine, lymphopenia, hypophosphatemia, thrombocytopenia, elevated AST, and leukopenia.
Strong inducers of CYP3A4/5 and inhibitors of CYP3A4 may affect concentrations of the primary metabolite of Torisel. If alternatives cannot be used, dose modifications of Torisel are recommended.
Please see TORISEL full prescribing information at http://www.wyeth.com
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