Bevacizumab and QoL in Advanced Ovarian Cancer
At present, only one antiangiogenetic drug, bevacizumab, has been tested in large first-line studies. The recent Phase III trial indicates that bevacizumab provides a PFS benefit when used in combination with first-line carboplatin–paclitaxel chemotherapy and continued as maintenance therapy for 12 months, but at the price of a small but clinically relevant reduction in patient QoL during the maintenance phase. Further studies of bevacizumab–chemotherapy combinations are warranted to optimize the dose and duration of maintenance therapy, and to identify the best clinical setting (first line, relapse or both) for this drug, and all these aspects need to be weighed with the impact of the therapy on patients' QoL.
A number of other antiangiogenic agents, including vascular disrupting agents, angiogenesis inhibitors and multitarget tyrosine kinase inhibitors are under evaluation and clinical trials with these new agents are ongoing or have been recently concluded; however, complete results are not yet available and the most promising combinations of antiangiogenic agents with standard chemotherapy require further exploration. Of note, the new agents that can be orally administered are expected to interfere less with women's lives as compared with the continuative delivery of intravenous therapy.
Overall, although the strategy of inhibiting angiogenesis in ovarian cancer remains promising, antiangiogenic therapy is still faced with several open questions, such as the lack of accurate predictors of therapeutic efficacy, the inability to prevent resistance to treatment and several pharmacoeconomic concerns.
In the event that these trials are successful, which is plausible since angiogenesis is the driving pathway of most solid tumors, clinicians should rethink the whole strategy of ovarian cancer treatment and, in the absence of a definite predictive biomarker able to compel a strategy of individualized medicine, the combination of a better therapeutic index and a smaller negative impact on patients' QoL will be the winner of the competition.
Future Perspective
At present, only one antiangiogenetic drug, bevacizumab, has been tested in large first-line studies. The recent Phase III trial indicates that bevacizumab provides a PFS benefit when used in combination with first-line carboplatin–paclitaxel chemotherapy and continued as maintenance therapy for 12 months, but at the price of a small but clinically relevant reduction in patient QoL during the maintenance phase. Further studies of bevacizumab–chemotherapy combinations are warranted to optimize the dose and duration of maintenance therapy, and to identify the best clinical setting (first line, relapse or both) for this drug, and all these aspects need to be weighed with the impact of the therapy on patients' QoL.
A number of other antiangiogenic agents, including vascular disrupting agents, angiogenesis inhibitors and multitarget tyrosine kinase inhibitors are under evaluation and clinical trials with these new agents are ongoing or have been recently concluded; however, complete results are not yet available and the most promising combinations of antiangiogenic agents with standard chemotherapy require further exploration. Of note, the new agents that can be orally administered are expected to interfere less with women's lives as compared with the continuative delivery of intravenous therapy.
Overall, although the strategy of inhibiting angiogenesis in ovarian cancer remains promising, antiangiogenic therapy is still faced with several open questions, such as the lack of accurate predictors of therapeutic efficacy, the inability to prevent resistance to treatment and several pharmacoeconomic concerns.
In the event that these trials are successful, which is plausible since angiogenesis is the driving pathway of most solid tumors, clinicians should rethink the whole strategy of ovarian cancer treatment and, in the absence of a definite predictive biomarker able to compel a strategy of individualized medicine, the combination of a better therapeutic index and a smaller negative impact on patients' QoL will be the winner of the competition.
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