Response to bevacizumab combination chemotherapy of malignant pleural effusions associated with non-squamous non-small-cell lung cancer

Abstract

Malignant pleural effusion (MPE) is a common complication of lung cancer with devastating consequences. Since vascular endothelial growth factor (VEGF) has been implicated in MPE, we hypothesized that bevacizumab, an anti-VEGF antibody, may be effective against MPE in patients with non-small-cell lung cancer (NSCLC). We analysed the records of 21 patients treated for NSCLC-associated MPE between February, 2010 and August, 2013 who consequently underwent bevacizumab combination chemotherapy at the Institute of Biomedical Research and Innovation Hospital. The results were retrospectively analysed using case records and radiographic imaging records. Three patients exhibited complete response of the pleural effusion to bevacizumab treatment, 8 patients achieved a partial response (PR) and 6 patients showed no response. When efficacy was assessed by the response of the measurable primary or metastatic lesions to the treatment, 5 patients achieved a PR, 13 patients had stable disease and 3 patients exhibited progressive disease. The response rate (RR) of the pleural effusion to the antibody treatment was 71.4% and the overall RR of measurable lesions was 23.8%. The median time-to-response for pleural effusion was 132 days. In conclusion, this study demonstrated a high R R to bevacizumab combination therapy for the MPE associated with non-squamous NSCLC. Therefore, bevacizumab therapy may be considered a therapeutic option for patients with non-squamous NSCLC who develop MPE.

Outcomes of bevacizumab combined with chemotherapy in lung adenocarcinoma‐induced malignant pleural effusion

“…Bevacizumab has been reported to reduce the accumulation of MPE in animal models . The use of bevacizumab with chemotherapy to treat MPE has been explored in small‐scale clinical trials . Although this therapy seemed effective, the long‐term influence of combined therapy has not received sufficient attention.…”

“…Other studies have demonstrated the efficacy of chemotherapy plus bevacizumab in NSCLC‐related MPE. Masago et al reported a 71.4% (15/21) response rate of pleural effusion, while Kitamura et al revealed that 92.3% (12/13) of patients achieved MPE control lasting > 8 weeks after treatment with bevacizumab plus chemotherapy . A phase II study including 23 patients with NSCLC‐induced MPE administered bevacizumab with carboplatin‐paclitaxel therapy, yielding an MPE control rate of 91.3% .…”

“…Therefore, it was concluded that bevacizumab therapy was beneficial and sustained activity to control MPE. In addition, anti‐VEGF therapy may be more effective for malignant effusion than for measurable tumors …”

“…Bevacizumab, a humanized monoclonal antibody against VEGF, is reported to be effective in intrapleural therapy of malignant pleural fluid . In previous reports from Japan, an intravenous injection of bevacizumab plus chemotherapy was also shown to successfully block the accumulation of MPE in advanced NSCLC, with an MPE response rate of 71.4% and MPE control rate of approximately 92% . However, studies on long‐term outcomes of bevacizumab therapy for the control of MPE have not been intensive.…”

Antiangiogenic Therapy in Pancreatic Neuroendocrine Tumors

“…Its efficacy has been also demonstrated in an in vitro model of pNETs (26). Bevacizumab showed anti-tumor activity and efficacy both in monotherapy and in combination with interferon in metastatic renal cell carcinoma (27) or chemotherapy in metastatic colorectal cancer (28), lung (29) and breast (30) cancer, thus obtaining the approval by pharmaceutical authorities.…”