NEW ORLEANS, June 5 /PRNewswire/ -- Initial findings from a randomized phase III study, Cancer and Leukemia Group B (CALGB) Protocol 9840, demonstrate significant improvements in efficacy with weekly paclitaxel compared to paclitaxel administered every three weeks. Both response rate and time to disease progression were significantly better in the patients treated with the weekly regimen. The study also showed that the addition of trastuzumab did not significantly improve the efficacy of paclitaxel in patients with tumors that did not overexpress HER2. The findings were presented at the 40th American Society of Clinical Oncology (ASCO) Annual Meeting.
Principal Investigator, Andrew Seidman, MD, Associate Attending Physician, Breast Cancer Medicine Service, Memorial Sloan-Kettering Cancer Center, and Associate Professor at Cornell University Medical College, said "The results clearly demonstrate the superiority of weekly paclitaxel over the more conventional every third week dosing regimen, whether with trastuzumab for patients with HER2 positive breast cancer, or without it for those with HER2 negative breast cancer. These results are consistent with our prior observations, and the magnitude of the benefit has immediate implications for patient care. The use of weekly paclitaxel with trastuzumab for HER2 positive breast cancer is currently being studied in adjuvant trials for women with early stage breast cancer."
The primary aim of this study was two-fold. The first was to determine if weekly treatment with paclitaxel improves response rate compared to the standard every 3rd week regimen of paclitaxel regardless of the patients' HER2 status or use of trastuzumab. The second primary aim was to determine if the addition of trastuzumab to paclitaxel improves response rate compared to paclitaxel alone for patients with tumors that do not overexpress HER2. Secondary objectives were to evaluate time to progression and overall survival with respect to the above comparisons.
A total of 735 patients were included in the study (577 were treated and data from an additional 158 patients treated with every 3-week paclitaxel on a prior CALGB study were included in the 3-weekly paclitaxel analysis). Patients were randomized unequally (40:60) to receive paclitaxel 175mg/m2 every 3 weeks or weekly paclitaxel 80mg/m2.
While the study was enrolling patients, trastuzumab became standard therapy for patients with HER2 positive metastatic breast cancer. In the CALGB 9840 study, patients were assessed for HER2 status and those who had overexpression received trastuzumab, while those who had normal HER2 expression were randomized to receive trastuzumab or not with paclitaxel.
Initial findings showed a significant improvement in tumor response with weekly paclitaxel, with or without trastuzumab, compared to the every 3rd week regimen (40% vs 28%, p=0.017). The time to disease progression from the start of treatment was also significantly improved with the weekly therapy (9 months compared to 5 months, p=0.0008). There was also a trend toward longer survival for patients who received the weekly therapy (24 months compared to 16 months for those on the every 3rd week regimen (p=0.17)).
The weekly therapy caused less grade 3 neutropenia compared to the every 3rd week regimen (8% versus 15%, p=0.013), but more grade 3 sensory/motor neuropathy (23/8% versus 12/4%, p=0.001/0.04). Trastuzumab side-effects included four patients experiencing significant cardiac dysfunction. There were two treatment related deaths, both due to pneumonia in the weekly paclitaxel arm.
In the second analysis of this study that examined the use of trastuzumab in HER2 normal patients, the addition of trastuzumab did not significantly improve response rate (35% versus 29%), or time to disease progression (7 months versus 6 months). Overall survival was also similar regardless of trastuzumab use (22 months versus 20 months). Therefore it can be concluded that the addition of trastuzumab did not contribute to the efficacy of paclitaxel in patients with HER2 normal tumors.
"This study clearly demonstrates the significant impact that the change in treatment schedule from every 3rd week paclitaxel to weekly paclitaxel can have in the treatment of breast cancer," comments Richard L. Schilsky MD, Professor of Medicine, Associate Dean for Clinical Research, Biological Sciences Division, University of Chicago and Chairman, Cancer and Leukemia Group B. He added, "While trastuzumab is a valuable treatment for our patients who have HER2 positive advanced disease, this study does not support the use of trastuzumab in patients with HER2 normal tumors."
The Cancer and Leukemia Group B is an NCI-sponsored cooperative group of 250 institutions and more than 3000 oncology specialists that conducts cancer clinical trials in breast cancer, lung cancer, GI cancer, GU cancer, leukemia, lymphoma and melanoma. About 4000 patients are enrolled each year on 100 active protocols that address novel cancer treatment strategies, assess health-related quality of life and examine relationships between the molecular features of tumors and treatment outcomes.
For further information please contact:
Andrew Seidman, MD: (212) 639 5875
Richard Schilsky, MD: (773) 702-9753
John Easton, University of Chicago Media Relations: (773) 702-6241
Visit the CALGB website at: http://www.calgb.org/
Cancer and Leukemia Group B