Combining Antiangiogenics to Overcome Resistance: rationale and clinical experience
Cet article passe en revue les perspectives offertes par la combinaison d'agents anti-angiogéniques, reposant sur différents mécanismes d'action, pour combattre l'apparition d'une résistance thérapeutique dans les cancers métastasés
Antiangiogenic therapies are now well established in oncology clinical practice, however, despite initial optimism results of late phase trials, especially in the adjuvant setting, have largely proven disappointing to date. In the context of metastatic disease, resistance to antiangiogenic agents arises through a range of mechanisms, including the development of alternative angiogenic pathways. One of the proposed strategies to overcome this resistance is by combining antiangiogenic agents with different mechanisms of action. Early phase clinical trials assessing the tolerability and efficacy of different combinations of antiangiogenic drugs, including those which target the VEGF pathway, angiopoietins, as well as vascular disrupting agents are increasing in number. A promising example of this combination strategy is the combination of sorafenib and bevacizumab in different tumor types such as ovarian carcinoma or glioblastoma. However, overlapping and cumulative toxicity pose a real challenge. This review summarizes the preclinical rationale and current clinical experience in combining antiangiogenic therapies.