International Experts Panel Meeting of the Italian Association of Thoracic Oncology on Antiangiogenetic Drugs for Non–Small Cell Lung Cancer: Realities and Hopes

Abstract

Angiogenesis, one of the hallmarks of cancer, occurs when new blood vessels feed malignant cells, providing oxygen and nutrients, promoting tumor growth, and allowing tumor cells to escape into the circulation, thus leading to metastases. To date, a series of antiangiogenic drugs (either monoclonal antibodies or small molecules) have been approved by regulatory agencies for the treatment of advanced non-small cell lung cancer, and they are currently available for both first- and second-line therapy. The overall benefit of these drugs seems modest (although clearly significant), especially when administered as a single agent, and there is no clear consensus with regard to which patients should be candidates to receive these drugs across the different disease settings. From the biological perspective, angiogenesis represents a difficult and complex process to explore, given the interference with other key pathways and the dynamic evolution during the disease's history. Indeed, this process is complicated by the presence of multiple targets to hit, polymorphisms, hypoxia-dependent modifications, and epigenetics. These difficulties do not allow capture of which specific key pathways can be identified as biomarkers of efficacy so as to maximize to overall benefit of such drugs. An International Experts Panel Meeting was inspired by the absence of clear recommendations to address which patients should receive antiangiogenic drugs in the context of advanced non-small cell lung cancer so as to support decisions for clinical practice on a daily basis and determine priorities for future research. After a literature review and panelists consensus, a series of recommendations were defined to support decisions for the daily clinical practice and to indicate a potential road map for translational research.

LKB1 Expression Correlates with Increased Survival in Patients with Advanced Non–Small Cell Lung Cancer Treated with Chemotherapy and Bevacizumab

“…Medical treatment of lung cancer is prevalently not guided by the molecular tumor characteristics, both when using chemotherapy and when using antiangiogenic drugs like bevacizumab (21)(22)(23)(24).…”

“…Several efforts have been made to identify predictive biomarkers of sensitivity to bevacizumab, but none of them has been validated in clinical practice (25). This is likely related to the complexity of antiangiogenic effects both on tumor cells and on microenvironment (24). Remarkably, the possibility that a predictive biomarker of response to antiangiogenic therapy could be restricted to a specific tumor type has not been considered so far.…”

Antiangiogeneic Strategies in Mesothelioma

“…Although there has been over a decade of intense investigation, there are still no clear, validated biomarkers which predict the efficacy of bevacizumab or other anti-angiogenics, either in MPM or in other cancers (78). In the MAPS trial, the prognostic or predictive effect of baseline serum VEGF concentrations were assessed by ELISA in the 372/448 (83%) of patients with available samples.…”

UK newspaper reporting of the NHS cancer drugs fund, 2010 to 2015: a retrospective media analysis

“…The preponderance of stories on chemotherapy, 8 compared with surgery and radiotherapy, has probably contributed to a strong public perception that the best way to help cancer patients and improve outcomes is to allow them access to new (and expensive) medicines, whose performance is often hyped and gives rise to unreasonable expectations. [12][13][14][15] The reason for the preeminence of chemotherapy in cancer journalism is not clear but is likely to be related to the volume of press releases by both public and private sectors on the outputs of the global cancer research endeavour, which is disproportionally focused on fundamental cancer biology, new medicines and biomarkers. 16,17 In an era of 'alternative facts', it is imperative that health journalists maintain their credibility by being critical of the 'next big thing' or 'game changer' and that the research funders and institutions assist them in their work.…”