Closing faucets: the role of anti-angiogenic therapies in malignant pleural diseases.

ABSTRACT

Malignant pleural effusion (MPE) represents 15-35 % of pleural effusions and markedly worsens the prognosis and quality of life of patients with cancer. Malignant mesothelioma (MM) and lung adenocarcinoma are the most frequent primary and secondary causes, respectively, of MPE. Effective treatments for cancer-related MPE are warranted in order to improve symptoms, reduce the number of invasive pleural procedures, and prolong patient life. Since angiogenesis plays a key role in MPE development, the potential role of bevacizumab and other anti-angiogenic therapies have been explored in this review. No relevant phase III trials have specifically analysed the benefit from adding bevacizumab to platinum-based chemotherapy in lung cancer-related MPE. However, small retrospective series reported 71.4-93.3 % MPE control rate, a reduction in invasive procedures, and a safe profile with this combination. Being approved for the first-line treatment of non-squamous advanced NSCLC, the addition of bevacizumab should be considered for patients presenting with MPE. In addition, further studies in this are recommended. In MM, the addition of bevacizumab to platinum-based chemotherapy did not meet primary endpoints in two phase II trials. However, the beneficial results on OS reported in comparison with historical cohorts and the statistically significant benefit on PFS and OS observed in the phase III MAPS trial foretell an eventual role for the combination of platinum/pemetrexed/bevacizumab as front-line systemic therapy for pleural MM. To date, no other anti-angiogenic drug has showed significant benefit in the treatment of patients with either MPE or MM. However, new promising drugs such as ramucirumab or recombinant human endostar warrant further investigation.