Bevacizumab as first-line treatment of ovarian cancer: strengths and weaknesses of subgroup analyses

Abstract

Bevacizumab is approved as first-line treatment for ovarian cancer, in combination with carboplatin-paclitaxel, in patients with FIGO IIIb or IV disease, and as maintenance therapy. The results of subgroup analyses of data from the ICON7 study have resulted in bevacizumab use being restricted to “high-risk” patients in several countries. While a goal of obtaining as much information as possible from clinical trial data is understandable, there are also a number of limitations associated with subgroup analyses. Interpretation can be limited by the multiplicity of statistical tests (increasing the risk of false positive findings) and by low statistical power (increasing the chance of false negative results). In addition, the credibility of subgroup analyses is improved if they are restricted to the primary study outcome and limited to a small number of predefined patient subgroups. Overall, subgroup findings should be considered exploratory and hypothesis-generating. The subgroup analysis in ICON7 had a number of limitations, including post hoc definition of “high-“ and “lowrisk” groups, and questionable applicability of these definitions to clinical practice. Use of residual disease as a determinant of risk status is also problematic. Excessive emphasis on the role of subgroup analyses may lead to misunderstanding of the true results generated by the overall trial data, and support the incorrect selection of patients to be treated with the new or experimental therapy. Caution should be used in translating results of subgroup analysis to clinical practice guidelines.