110IN - Antiangiogenic therapies in the clinic: A double-edged sword?

Date 30 September 2012
Event ESMO Congress 2012
Session ESMO-EACR Joint symposium: Targeted therapies: Promises, successes and failures
Topics Anticancer agents
Therapy
Biological therapy
Presenter David Miles
Authors D. Miles
  • Medical Oncology, Mount Vernon Cancer Center, HA6 2 RN - Northwood/UK

Abstract

Despite the initial promise originally proposed by Judah Folkman and others, strategies aimed at tumour vasculature have met with variable success in the clinic. Antibodies and tyrosine kinase inhibitors targeting Vascular Endothelial Growth Factor (VEGF) are among the most highly developed agents targeting angiogenesis. In indications such as renal cell cancer, where alterations in VEGF are regarded as the principle oncogenic driver, VEGF inhibition has lead to clinically meaningful improvements in progression-free and overall survival. In more common epithelial malignancies, the efficacy VEGF inhibition has been more modest, possibly as a consequence of redundancy in the angiogenic process. The inherent complexity of the angiogenic response has also made it difficult to identify markers of efficacy, with a myriad of DNA, serological and dynamic (imaging) metrics being implicated in prognosis as well as prediction of treatment efficacy and toxicity, e.g., a second-generation assay of plasma VEGF appears to be of predictive benefit in a retrospective analysis of two studies in metastatic breast cancer and its use is being tested prospectively. The controversy surrounding the use of anti-angiogenic approaches in terms of efficacy and regulatory considerations, underscores the challenges in their development: e.g., simple clinical observations that in malignancies with a relatively long natural history, attributable alterations in progression-free survival are unlikely to be a surrogate for overall survival. Similarly, while the available data for the use of anti-angiogenic agents in the adjuvant treatment of cancer is clearly disappointing it is not perhaps surprising, given the likely lack of VEGF dependency of what we understand to be micro-metastatic disease. A clearer understanding of angiogenesis and its modulation will enable further rational development of this important modality.

Disclosure

The author has declared no conflicts of interest.