06 Jun Ovarian Cancer: Using a Genetic Signature To Predict Response to Bevacizumab
MedicalResearch.com Interview with:
Sean C. Dowdy, MD, FACS
Professor and Chair, Division of Gynecologic Surgery
Vice-Chair for Research, Department of Obstetrics and Gynecology
Co-Leader, Women’s Cancer Program
Mayo Clinic College of Medicine
MedicalResearch.com: What are the main findings of the study?
Dr. Dowdy: This study was a collaboration between four groups in 3 countries to determine if a genetic “signature” could predict which patients with ovarian cancer benefit from Bevacizumab (a very expensive drug with marginal benefit in patients with ovarian cancer). We hypothesized that while benefit may be marginal in a large group, patients with specific genetic changes could derive significant benefit from it. Using gene expression arrays (analyzing over 18,000 genes) we separated patients into four subgroups as described by The Cancer Genome Atlas (TCGA). We show that patients in the proliferative and mesenchymal groups had a 8-10 month improvement in outcome compared to a 3 month improvement for the other two groups (immunoreactive and differentiated).
MedicalResearch.com: Were any of the findings unexpected?
Dr. Dowdy: We hypothesized that patients with “angiogenic signatures” would benefit most from bevacizumab, because this drug inhibits angiogenesis (new vessel formation). The two molecular subtypes that benefited most (proliferative and mesenchymal) in fact have those angiogenic signatures. What we didn’t expect was the magnitude of the outcome difference. A 10 month improvement in progressive free survival is quite significant for patients with ovarian cancer (prior studies showed only a 2.5 month improvement).
MedicalResearch.com: What should clinicians and patients take away from your report?
Dr. Dowdy: Ever since the human genome was sequenced, our goal has been to individualize therapy for patients with cancer. This now appears to be within our grasp. We have shown that certain groups of patients respond better than others to this particular drug, and we can predict this before they receive treatment. Our results must be validated in other groups before our findings can be applied to patients outside a clinical trial, but our results suggest we can reduce side effects and cost by using this drug only in patients who are likely to benefit from it.
MedicalResearch.com: What recommendations do you have for future research as a result of this study?
Dr. Dowdy: One strength of our study is that we used molecular subgroups which have already been validated (TCGA). Another group in the United Kingdom developed new molecular subgroups and had similar findings. The next step is for our groups to work together to validate these results so they can be used for the best interest of women with ovarian cancer.