Massey physician-researcher helps develop and lead national breast cancer studies
VCU Massey Cancer Center physician-researcher Charles E. Geyer, Jr., M.D., co-developed and co-led two important national breast cancer clinical trials that were recently presented at the American Society of Clinical Oncology’s annual meeting in Chicago. One of the studies was selected for the “Best of ASCO” Program, which presents the scientific and educational highlights of the meeting.
The “Best of ASCO” study reported a joint analysis on what are known as the “ABC (Anthracyclines in early Breast Cancer) Trials,” which are three clinical trials that tested the effectiveness of a combination of the drugs docetaxel and cyclophosphamide (TC) against standard anthracycline/taxane-based chemotherapy (TaxAC) regimens in patients with high-risk, HER2-negative breast cancer. A total of 4,242 patients participated from clinical trials National Adjuvant Breast and Bowel Project (NSABP) B-46, NSABP B-49 and US Oncology Research Network (USOR) 06-090.
TaxAC regimens have represented the standard of care for high risk, HER negative breast cancers, but the anthracyclines in the regimen are associated with a low, but important risk for severe late complications such as acute leukemia and heart failure. An important but relatively small study previously conducted by USOR had shown TC was superior to AC in moderate-risk, HER2 negative breast cancer and effectively eliminates the risk for leukemia and hear failure. Therefore, the ABC trials were conducted to determine if TC was “non-inferior” to TaxAC in high-risk breast cancer.
Study findings were reported early since a planned interim analysis demonstrated that TC was actually inferior to the TaxAC regimens in the high risk patients entered in the ABC trials. Of interest, among patients with hormone receptor-positive breast cancer, lymph node status appeared to be important in determining if the TaxAC provided greater benefit than TC. In node-negative, hormone receptor positive patients, TC performed as well as TaxAC. With the increased risk associated with positive lymph nodes, TaxAC appeared more effective. In contrast, TaxAC was more effective in women with hormone receptor negative disease, irrespective of nodal status.
“This important study demonstrates that anthracyclines should remain an important component of adjuvant chemotherapy in women with high-risk breast cancer, and the study provides important information for physicians to help their patients determine if the benefits of including an anthracycline outweigh the risks” says medical oncologist Geyer, who led the development, conduct and reporting of the two NSABP trials and chaired the Scientific Steering Committee for the ABC trials initiative. Geyer is the associate director for clinical research and the Harrigan, Haw, Luck Families Chair in Cancer Research at Massey as well as professor in the Division of Hematology, Oncology and Palliative Care in the VCU School of Medicine. “Since these are initial findings from the study, we plan to continue following these patients to better define differences in long-term outcomes. We also plan extensive correlative science studies on the tumor specimens submitted by the patients on the trial to determine if we can more precisely define the individuals who actually benefit the most from the anthracycline.”
Geyer also led the reporting of five-year outcomes of the NSABP B-41 phase 3 clinical trial. The NSABP B-41 trial tested the beneficial effects of a second HER2-targeted drug, lapatinib (also known as Tykerb), in patients with HER2-positive breast cancer who had not yet had surgery. The trial evaluated combining lapatinib with trastuzumab or substitution of lapatinib for trastuzumab in combination with a standard neoadjuvant (treatment prior to surgery) therapy of weekly paclitaxel following anthracycline-based chemotherapy.
The combination of lapatinib and trastuzumab resulted in slightly increased pCR rates, which is the absence of residual disease in the breast and axillary lymph nodes at the completion of neoadjuvant treatment. Increased pCR rates translated to longer recurrence-free intervals and better overall survival, though the increase was not great enough to be statistically significant. In hormone receptor-negative patients, however, the improvement was more remarkable.
“While the study did not prove that adding lapatinib to trastuzumab was better than trastuzumab alone, it did suggest that combining HER2-targeted therapies may be particularly beneficial to hormone receptor-negative patients,” says Geyer. “Results from studies like these help us move toward personalizing cancer therapies based on the unique characteristics of each tumor.”