In the past decade researchers and pharmaceutical companies have become more aware of the need to understand treatment side effects, as well as a drug’s effectiveness. Reducing patients’ symptom burdens means that they may survive with reasonable quality of life.
To understand the symptom burden of bevacizumab, two MD Anderson investigators joined a large, national, multicenter Phase III trial, under the auspices of the Radiation Therapy Oncology Group: Jeffrey Wefel, Ph.D., associate professor in Neuro-Oncology, a senior author on the study, and Terri Armstrong, Ph.D., adjunct professor in the same department and professor at The University of Texas Health Science Center at Houston School of Nursing.
The objective was to understand the clinical benefit of adding bevacizumab to standard chemotherapy and radiation with maintenance temozolomide, versus those who received a placebo and standard treatment. Instead of the traditional overall survival (OS) and progression-free survival (PFS) endpoints, however, they wanted to understand the potential impact on patients’ quality of life.
Using objective tests of cognitive function and subjective measures of symptoms, 507 patients were evaluated at diagnosis and at intervals throughout treatment, as long as scans showed their tumors were not progressing.
Putting the total picture together
At the beginning of the study, patients’ neurocognitive function in both groups was below healthy population norms. Analyses showed those treated with bevacizumab, compared to those treated with the placebo, demonstrated greater decline in global neurocognitive function, executive function (skills like planning, organizing and multi-tasking) and thought processing speed. In addition, patients’ subjective report of symptoms and the interference of these symptoms with their daily life were greater in those treated with bevacizumab.
Additionally, baseline performance and early change (through week 10) in symptoms, quality of life and neurocognitive function were prognostic for both PFS and OS.
“We found that patients with worse cognitive function at baseline, and those who experienced cognitive decline after concurrent chemotherapy and radiation — with or without bevacizumab — were at greater risk for shorter PFS or OS time,” Wefel says.
“The idea of our research was to put together the total picture of this treatment, not only how it affects the tumor, but how it affects patients and how they go about their lives,” Armstrong says. “It was our hope that this treatment would improve life for them, but that just wasn’t the case. For many, both tumor and treatment-related symptoms were worse and continued to get worse over time.”
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