sanofi-aventis announced that a meta-analysis of individual patient data (IPD) including 2,867 patients from seven clinical trials demonstrated a significant overall survival (OS) benefit of Taxotere (docetaxel injection concentrate) over vinca-alkaloid-based regimens in the treatment of first line advanced Non Small Cell Lung Cancer (NSCLC) patients. Efficacy results of this IPD meta-analysis, called DOCMA-LC (DOCetaxel Meta-Analysis in Lung Cancer), were presented at the 12th World Conference on Lung Cancer in Seoul, South Korea, as a proffered paper.
The aim of DOCMA-LC was to assess the overall survival and tolerability as well as to validate surrogate endpoints from all randomized clinical trials (RCT) comparing Taxotere-based chemotherapy to vinorelbine- or vindesine-based chemotherapy regimens in first-line treatment of advanced NSCLC. The findings of DOCMA-LC announced confirm the significant superiority of Taxotere-based regimens compared to vinca-alkaloid regimens in terms of overall survival (HR: 0.90; 95%CI [0.82;0.98]). A multivariate analysis strongly confirmed this benefit of Taxotere-based regimens (HR: 0.88; 95%CI [0.80; 0.97]).
Tolerability also favoured Taxotere- based regimens as mentioned in a previous published meta-analysis presented at ASCO (American Society of Clinical Oncology) 20061 and currently in press with the Journal of Thoracic Oncology. In the IDP meta-analysis, tolerability, as well as surrogate end-points, are still under analysis.
"This individual patient data meta-analysis provides the evidence that one third-generation agent, Taxotere, is significantly superior to vinca-alkaloid regimens, in the first-line treatment of patients with 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.
Taxanes and vinca-alkaloids are commonly used agents, in first-line therapy of advanced NSCLC. The TAX 326 study demonstrating a benefit in median Overall Survival (OS) of docetaxel-cisplatin over vinorelbine-cisplatin was the basis of the European and US registration of Taxotere in first line advanced NSCLC. As some data in comparative studies have suggested consistent benefit in survival and safety, a meta-analysis was performed in order to assess this potential benefit of Taxotere-based regimens in comparison with vinca-alkaloidbased regimens, in terms of Overall Survival (OS) and tolerability.
DOCMA-LC aimed to assess OS and tolerability and to validate surrogate endpoints from all randomized clinical trials (RCT) comparing Taxotere-based chemotherapy to vinorelbine- or vindesine-based chemotherapy in first-line advanced NSCLC.
The first survival results1 for all drug combinations favoured Taxotere with an HR of 0.87 (95% CI, 0.79-0.96) for Taxotere combined with a platinum agent; 0.89 (95% CI, 0.82-0.96) for nonplatinum-based Taxotere regimens; 0.96 (95% CI, 0.81-1.13) for Taxotere combined with gemcitabine; and 0.87 (95% CI, 0.69-1.09) for Taxotere monotherapy.
The individual patient data meta-analysis (DOCMA-LC) confirmed the Taxotere benefit in OS with a 10% reduction of the risk of death (HR: 0.90; 95%CI [0.82; 0.98]). The pooled estimate for overall survival showed an improvement in favour of Taxotere® whatever the data used.
Tolerability was assessed and also favoured Taxotere-based regimens in a previous published and unpublished meta-analysis presented at ASCO 2006 and currently in press with the Journal of Thoracic Oncology 9 and further tolerability, as well as surrogate end-points, are still underanalysis in the IDP meta-analysis.
Taxotere is currently approved in 5 different cancer types in Europe and the US.
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 doxorubicin 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, nodepositive 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 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 also is approved, as a single agent, for patients with unresectable locally advanced or metastatic NSCLC after failure of prior platinum-based chemotherapy.
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.
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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 2006, the use of Taxotere Injection Concentrate in combination with cisplatin and fluorouracil for the treatment of patients with advanced stomach (gastric) cancer, including cancer of the gastro oesophageal (GE) junction, who have not received prior chemotherapy for advanced disease.
In October 2006, the European Medicines Agency (EMEA) and the FDA approved Taxotere (docetaxel) Injection Concentrate in combination with cisplatin and fluorouracil for the induction treatment of patients with inoperable locally advanced squamous cell carcinoma of the head and neck (SCCHN).