Results of a meta-analysis show benefits of Taxotere® (docetaxel) regimens in patients with advanced non-small cell lung cancer (NSCLC)

Findings show demonstrated overall survival with less febrile neutropenia for Taxotere® versus vinca-alkaloid regimens. Sanofi-aventis announced today that a meta-analysis performed on seven clinical trials in patients with advanced non-small cell lung cancer showed that patients receiving Taxotere® (docetaxel) Injection Concentrate had demonstrated overall survival and less febrile neutropenia than those treated with vinca-alkaloid (vinorelbine or vindesine) regimens. The trials used Taxotere® and vinca-alkaloids alone or in combination as first-line therapy for advanced non-small cell lung cancer. Six of the trials compared Taxotere® to vinorelbine regimens and one to a vindesine regimen. The results of the meta-analysis will be presented at the 42nd Annual Meeting of the American Society of Clinical Oncology (ASCO), in Atlanta, Georgia. The pooled results of the seven trials conducted on a total of 2867 patients show that Taxotere® regimens significantly improved Overall Survival (OS) (Hazard Ratio (HR) = 0.89, 95% confidence interval (CI) [0.82;0.96], p=0.03) compared to vinca-alkaloid regimens in this patient population. The comparison was done on a total of 1638 patients who received Taxotere® regimens and 1229 who received vinca-alkaloid regimens. The meta-analysis also demonstrated that the benefit derived from Taxotere therapy persisted after exclusion of the vindesine study (HR =0.90 [0.83; 0.98]) and also when monotherapy regimens were excluded from the analysis (HR = 0.89 [0.82; 0.97]). While neutropenia was a common adverse event in the trials, it was significantly less frequent with Taxotere (Odds Ratio* (OR) = 0.60; 95%CI [0.39; 0.92, p=0.019]) than with vinca-alkoloid regimens, as was febrile neutropenia, a condition marked by fever and decrease in the number of a type of white blood cells that helps fight infection, (OR= 0.60 [0.39; 0.96], p=0.034). "This is the first meta-analysis that demonstrated significant benefits in both survival and in toxicity for patients receiving Taxotere-based chemotherapy compared to vinca alkaloid-based regimen in first-line advanced NSCLC," said Jean-Yves Douillard, Professor and Head of the Department of Medical Oncology at the Centre R Gauducheau in Saint Herblain, France, and principal investigator of the meta-analysis. The findings of the meta-analysis are in line with the results of the pivotal TAX 326 study, which provided the basis for the Taxotere approval in the first-line treatment of non- small cell lung cancer. About the meta-analysis As some data in comparative studies have suggested possible differences in survival and safety, an exhaustive meta-analysis was performed on published and unpublished data to assess the potential benefit of Taxotere based regimens in comparison with vinca alkaloid-based therapy regimens, in terms of overall survival and toxicity. MEDLINE, CANCERLIT and Cochrane Library searches were supplemented by information from clinical study reports and manual searching of relevant meeting proceedings. Only randomized trials comparing Taxotere-based chemotherapy to vinorelbine or vindesine based chemotherapy were included. Outcomes recorded were Overall Survival and neutropenia. Fixed effects models were used to estimate the pooled hazard ratio (HR) and the odds ratio (OR) of neutropenia. An HR or OR less than 1 indicates that Taxotere is superior to vinca alkaloids. Heterogeneity was assessed using the Cochran Q-test. * Odds Ratio: The “odds” of an event is the ratio of the chance of it occurring to the chance of it not occurring. The odds ratio is a measure of the relative benefit of the experimental treatment, comparing the odds of an event in the intervention group to the odds of an event in the control group. About Lung Cancer • Lung cancer has been the most common cancer globally since 1985 and, in 2002, 1.35 million new cases of lung cancer were diagnosed, which represents about 12.4% of all newly diagnosed cancers. • Lung cancer accounts for 29% of all cancer deaths and causes more deaths than breast, colorectal and prostate cancer combined. There are an estimated 1.18 million lung cancer deaths annually. • In the US, the most recently available figures from 2002 show that 100,099 men and 80,163 women were diagnosed with lung cancer. In the European Union (EU), lung cancer is the third most commonly diagnosed cancer, with 243,600 people diagnosed in the year 2000. Lung cancer does not only affect developed nations; nearly 50% of lung cancer cases in 2002 were reported in developing countries. • Among US men, incidence rates have significantly declined since 1984 from 102.0 per 100,000 in 1984 to 77.8 per 100,000 in 2002. Since 1998, the lung cancer rates in women have stabilised after a long period of increase. About TAXOTERE® Taxotere® is currently approved in 4 different indications: In Breast Cancer • In the United States and in Europe, Taxotere® is approved to treat patients with locally advanced or metastatic breast cancer after failure of prior chemotherapy. It is also approved in Europe in combination with doxorubicine for patients who have received prior cytotoxic therapy for this condition and in combination with capecitabine after failure of cytotoxic therapy which would have included anthracycline. In the adjuvant setting (post surgery) it is approved in the US and in Europe in combination with doxorubicin and cyclophosphamide (TAC regimen) for the treatment of patients with operable, node-positive breast cancer. Finally, in Europe, Taxotere® is approved in combination with trastuzumab for the treatment of patients with metastatic breast cancer- overexpressing Her2 receptor. In Lung Cancer • In the US and in Europe, Taxotere®, in combination with cisplatin, is approved for the treatment of patients with unresectable locally advanced or metastatic non-small cell lung cancer (NSCLC) who have not received prior chemotherapy, and it is also approved as a single agent, for patients with unresectable locally advanced or metastatic NSCLC after failure of prior platinum-based chemotherapy. In Prostate cancer • Taxotere® is approved for use in combination with prednisone as a treatment for androgen-independent (hormone-refractory) metastatic prostate cancer in the US and in Europe. In Gastric (Stomach) cancer • The FDA and the Committee for Medicinal Products for Human Use (CHMP) of the European Agency for the Evaluation of Medicinal Products (EMEA) approved in march 2005, the use of TAXOTERE® Injection Concentrate in combination with cisplatin and 5-fluorouracil for the treatment of patients with advanced stomach (gastric) cancer, including cancer of the gastro oesophageal junction, who have not received prior chemotherapy for advanced disease. About sanofi-aventis Sanofi-aventis is the world’s third largest pharmaceutical company, ranking number one in Europe. Backed by a world-class R&D organisation, sanofi-aventis is developing leading positions in seven major therapeutic areas: cardiovascular, thrombosis, oncology, metabolic diseases, central nervous system, internal medicine and vaccines. Sanofi-aventis is listed in Paris (EURONEXT: SAN) and in New York (NYSE: SNY). 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