Sanofi-aventis said a study showed improved survival among women with early stage breast cancer who have had surgery and treatment with the Taxotere-based (docetaxel) chemotherapy compared to standard chemotherapy.
The study results were presented at the 30th annual San Antonio Breast Cancer Symposium (SABCS).
The presentation reports results with a median follow-up of 7 years and has been updated since the last report was published with 5.5 years median follow-up [Jones S et al. J Clin Oncol, 2006, 24:5381-7]. This latest report has also been updated from the abstract submitted to SABCS 2007.
In the updated analysis, overall survival at 7 years was statistically higher among women treated with Taxotere and cyclophosphamide (TC) versus those treated with doxorubicin and cyclophosphamide (AC): 87 per cent versus 82 per cent (HR: 0.69, [95 per cent CI, 0.50, 0.97]). The 31 per cent reduction in the risk of death was statistically significant (p=0.032). At 7 years, the disease-free survival (DFS) was also statistically greater among women treated with TC than those treated with AC: 81 per cent versus 75 per cent (HR: 0.74, [95 per cent CI, 0.56, 0.98]). The 26 per cent reduction in the risk of cancer recurrence among women treated with TC was statistically significant (p=0.033). The disease-free survival benefit seen in the elderly patients (aged 65 years or older; 31 per cent risk reduction of recurrence) is consistent with that in the overall patient population.
The regimen combining the anthracycline doxorubicin with cyclophosphamide became a foundation of breast cancer chemotherapy for more than 30 years.
"The invest igational Taxotere combination significantly increased the percentage of women living with no signs of cancer at 7 years, as compared to the anthracycline combination," said Dr. Stephen Jones, Principal study investigator, medical director and co-chair, breast cancer research committee of US Oncology
USO Adjuvant Trial 9735 was designed primarily to evaluate disease-free survival among women with node-positive and node-negative early breast cancer. Node-positive indicates that the cancer has spread to the lymph nodes under the arm, while node-negative breast cancer means that the lymph nodes are clear of cancer. Secondary endpoints included overall survival and safety. The investigators also explored the efficacy and safety of the treatments based on the age of patients and the biologic characteristics of their tumors.
All patients taking part in the study had received surgery for Stage I-III invasive breast cancer, meaning that the cancer was either localized to the breast or had spread to the lymph nodes under the adjacent arm.
A total of 1016 patients were randomized between June 1997 and December 1999; 48 per cent of patients had node-negative disease and 16 per cent were age 65 years or older. After surgery, patients were randomized to receive four cycles of either standard-dose of anthracycline doxorubicin 60 mg/m 2 and cyclophosphamide 600 mg/m 2 (n=510) or Taxotere ® 75 mg/m 2 and cyclophosphamide 600 mg/m 2 (n=506), administered by intravenous infusion every three weeks. After chemotherapy was completed, patients were treated with radiation therapy if indicated. Patients with hormone receptor positive disease also received hormonal therapy (tamoxifen).
In the TC group, there were 88 DFS events (17 per cent) and 58 deaths (12 per cent). The AC group had 118 DFS events (23 per cent) and 84 deaths (17 per cent). Exploratory analyses showed benefit of TC irrespective of age, hormonal status or Her2 status. Grade 3-4 neutropenia occurred in 60 per cent of younger (<65 years) and 52 per cent of older (¡Ý65 years) women in the TC group, and in 54 per cent and 59 per cent of younger and older women, respectively, in the AC group. Among younger patients, the frequencies of Grade 3-4 febrile neutropenia were 4.4 per cent with TC and 2.3 per cent with AC, while in older patients the frequencies were 7.7 per cent and 3.7 per cent for TC and AC, respectively. Grade 3-4 nausea was less common among women in both age groups treated with TC (<65 years: 2 per cent, ¡Ý65 years: 3 per cent) than those given AC (<65 years: 7 per cent,¡Ý65 years: 5 per cent). In the TC group, additional Grade 3-4 adverse events reported among women <65 and ¡Ý65 were Grade 3-4 fever in 4 per cent and 6 per cent and Grade 3-4 infection in 7 per cent and 6 per cent, respectively, while in the AC arm the rates of Grade 3-4 fever were 3 per cent and 4 per cent and Grade 3-4 infections were 10 per cent and 2 per cent for younger and older women, respectively.
Breast cancer is the most frequently diagnosed cancer in women throughout the world. By the end of 2007, more than 178,000 American women will have learned they have invasive breast cancer. In the European Union (EU) , more than 429,900 new cases were diagnosed in 2006. Age is the biggest risk factor, and one in 26 women over 70 will have breast cancer in her lifetime.
US Oncology, headquartered in Houston, Texas, supports one of the nation's largest cancer treatment and research networks. US Oncology also provides a broad range of services to pharmaceutical manufacturers, including product distribution and informational services such as data reporting and analysis.
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 not 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 the 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.
In the US and Europe, Taxotere in combination with cisplatin and 5-fluorouracil is approved for the treatment of patients with advanced stomach (gastric) cancer, including cancer of the gastro-esophageal (GE) junction, who have not received prior chemotherapy for advanced disease.
The European Medicines Agency (EMEA) and the FDA approved Taxotere 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). In September 2007, the FDA extended this approval to include patients with locally advanced SCCHN prior to chemoradiotherapy and surgery. In November 2007 EMEA gave its approval for the use of Taxotere for the induction treatment of patients with locally advanced squamous cell carcinoma of the head and neck.
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