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Breast Cancer
Meta-analysis of Bevacizumab Trials in Breast Cancer Show Longer PFS By Caroline Helwick
CHICAGO—The benefit of bevacizumab in metastatic breast cancer was made clear in a meta-analysis of key trials presented by Joyce O’Shaughnessy, MD, of Baylor-Sammons Cancer Center and US Oncology, during the 2010 annual meeting of the American Society of Clinical Oncology. Three randomized trials—E2100, AVADO, and RIBBON-1—that include a total of 2447 patients have demonstrated significantly improved progression-free survival (PFS) for bevacizumab combined with different chemotherapy regimens for frontline treatment of metastatic breast cancer. In the pooled analysis, median PFS improved by 2.5 months when bevacizumab was combined with chemotherapy compared with chemotherapy alone, regardless of hormone receptor status, sites of metastasis, disease-free interval, or prior adjuvant taxane use, O’Shaughnessy said. The chemotherapy regimens for metastatic breast cancer included weekly paclitaxel; every-3-week docetaxel; and capecitabine, docetaxel or nanoparticle albumin-bound (nab)-paclitaxel, and doxorubicin or epirubicin. Approximately 50% had received adjuvant therapy. Median follow-up was 23 months to 35 months. An overview of efficacy is shown in the Table. O’Shaughnessy and colleagues pooled the individual results and arrived at an
overall PFS of 9.2 months with bevacizumab versus 6.7 months with chemotherapy alone, for a 36% reduction in risk. All subgroups derived benefit from bevacizumab, including patients with adverse prognostic features. Response rates increased by an absolute 17% versus controls. Overall survival (OS), however, was not significantly improved in either the individual trials or the pooled analysis. In the pooled population, OS was 26.7 months with bevacizumab and 26.4 months with chemotherapy alone; 1year survival rates were 82% and 77%, respectively. There were no survival differences by subsets. “But in general, patients received multiple treatments upon progression,” O’Shaughnessy noted, which has a wellknown effect on survival and thus makes it very difficult to show survival differences between arms. In the nonbevacizumab arms, 71% of patients received additional chemotherapy after the study, as did 65% of patients in the bevacizumab arm. O’Shaughnessy pointed out that 50% of the chemotherapy-alone arm received bevacizumab. An additional four anticancer agents were given to 25% of patients. Bevacizumab use has been proved safe, with treatment-related deaths reported for 2.1% of patients. Grade 3 or higher adverse events included neutropenia, sensory neuropathy, and
Table Efficacy of Bevacizumab in Individual Trials Trial
Median PFS Non-BV arm BV arm
HR
P
E2100
5.8
11.3
0.48
<.001
AVADO
7.9
8.8
0.62
<.001
RIBBON-1 (capecitabine)
5.7
8.6
0.69
<.001
RIBBON-1 (taxane/anthracycline)
9.0
9.2
0.64
<.001
BV indicates bevacizumab; HR, hazard ratio; PFS, progression-free survival.
hypertension in approximately 10% of patients; febrile neutropenia in 6.5% of patients; venous thromboembolism in 2.8% of patients; and proteinuria in 2.3% of patients. OS benefit uncertain Hope Rugo, MD, of the University of California, San Francisco, posed some reasons for the lack of OS benefit shown in the trials. “Line of therapy is important,” she pointed out. Studies are less likely to show a survival benefit in the first-line unselected population, whose biology is “extremely heterogeneous.” Late-line studies are more likely to enroll a more homogeneous group of patients who have likely responded to prior treatments, have a good performance status, and have tumors associated with rapid relapse, which makes development of resistance less likely, she said.
In addition, observation of an OS benefit is dependent on survival time postprogression, and short follow-up as well as crossover treatments (50% of the control group received bevacizumab) make it highly unlikely for this to be observed. Rugo said the future studies need to hone in on which patients are more likely to benefit from taking bevacizumab. “Collaborative research and tumor biopsies are required to answer the critical question of which patients benefit most from antiangiogenic therapy,” she concluded. ●
Did You Know? The number of prescription drugs abandoned by patients at the pharmacy rose 55% in the second quarter of 2010 compared with 4 years earlier, The Wall Street Journal reports.
PHARMACY CAREERS
Business Management Programs Help Clinicians Improve Healthcare Delivery By Eileen Koutnik-Fotopoulos
H
ealthcare is more than medicine and patient care. Physicians, pharmacists, nurses, and hospital administrators are realizing that healthcare is also a business. As a result, healthcare professionals are looking for ways to improve quality of care while lowering costs. College and universities are answering the call with business management courses geared toward medical professionals. “Healthcare has traditionally set itself apart from other industries. It’s extremely important to take best practices from across all industries and disciplines and learn everything we can to deliver the highest quality of care more efficiently,” says Judy Smith, MD, FACS, medical
www.theOncologyPharmacist.com
director for the Roswell Park Cancer Institute in Buffalo, New York. The cost of cancer care and how to best treat the disease are concerns for clinical professionals treating cancer patients. “The high cost of cancer care in general is an issue. Our patients and providers have high expectations, and we have to learn how to manage the business of cancer better,” explains Smith. She notes how cancer is treated by providers has changed. “It’s not just managing acute cancer but also longterm care.” Furthermore, the demand for cancer care is increasing because “of the aging population and the high number of cancer survivors,” adds Smith.
In an effort to improve Roswell Park’s operations and optimize patient care, Smith is one of 68 students enrolled in Harvard Business School’s Managing Healthcare Delivery executive education program. Launched in October 2009, the $22,000 nondegree program consists of three 1-week sessions over 9 months. “More and more clinicians, particularly clinical leaders, are recognizing that a significant portion of their job is not only to deliver excellent care, but also to manage and allocate resources appropriately,” says Cara M. Sterling, director of the healthcare initiative at Harvard Business School. “Clinicians tend to be fact-based
learners who appreciate the body of knowledge related to managing people, applying information technologies, and understanding and designing management metrics, to name just a few, that business schools have to offer. The majority, however, don’t have 2 years to invest in an MBA program. This program was developed specifically for healthcare delivery professionals who want an immersive management education experience, but want to do it in the context of their current job,” explains Sterling. Sessions cover developing effective operational models, teams, and delivery strategies; managing performance of Continued on page 25
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