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Q&A:
Clinical Benefits of Anti-Angiogenic Agents in First-Line NSCLC: Benchtop to Clinical Practice
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Nicholas Professor in Medical Oncology School of Cancer and Imaging Sciences University of Manchester Department of Medical Oncology Christie Hospital NHS Trust Manchester, United Kingdom |
Dr. Thatcher provides expert feedback to physician questions on this topic. These questions were submitted by participants in a multimedia activity.
- How do you treat patients with non–small-cell lung cancer (NSCLC) and CNS metastases? Is the combination of bevacizumab and chemotherapy an option?
- What is the appropriate dose when adding bevacizumab to the treatment regimen for patients with NSCLC? Can you explain how you make your decision?
- How would you manage the bleeding side effects in patients taking bevacizumab?
- Do you feel that bevacizumab works better in combination with certain chemotherapy regimens (for example, taxanes)?
- What specific cautions would you take when treating a hypertensive patient with NSCLC?
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How do you treat patients with non–small-cell lung cancer (NSCLC) and CNS metastases? Is the combination of bevacizumab and chemotherapy an option? | |
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It is possible to treat patients with CNS metastases (which have been previously treated and stabilised) with subsequent chemotherapy and bevacizumab. Indeed, the licence in the EU has removed the contraindication for bevacizumab in patients with CNS metastases. The change was based on a retrospective report of 639 patients with brain metastases from differing primary sites, including NSCLC (Besse B. Clin Cancer Res. 2010;16:269-278). The CNS metastases were either known at study outset but had been treated or had developed, or were identified during the course of the trials. These datasets included the E4599, AVAiL, and the SAiL trials, and 2 trials in which treated CNS metastases were allowed at study entry, namely the ATLAS trial and the PASSPORT trial. PASSPORT was a prospective phase 2 study which enrolled 115 patients with NSCLC and treated CNS metastases; there were no episodes of cerebral haemorrhage. | |
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What is the appropriate dose when adding bevacizumab to the treatment regimen for patients with NSCLC? Can you explain how you make your decision? | |
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Bevacizumab can be used with a platinum-containing chemotherapy at 7.5 or The other large database is the SAiL study, which allowed either dose to be used In this trial the median survival was |
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How would you manage the bleeding side effects in patients taking bevacizumab? | |
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The available data on bleeding events with bevacizumab-treated patients across multiple tumour types can be seen from the package insert (Avastin [package insert]. Genentech; South San Francisco, CA; 2009). It should be noted that the majority of bleeding events, particularly in the SAiL trial, were mild epistaxis. Almost all the bleeding events were mild and resolved very quickly (Dansin E et al. Eur J Cancer. 2009;7:556[abstract 9168]). In NSCLC, the risk factors which must be identified and in which bevacizumab would be contraindicated include squamous cell histology and recent haemoptysis. Bevacizumab should be discontinued in patients with haemorrhage and appropriate intervention to control the haemorrhage instituted. Bevacizumab should be discontinued permanently in patients who experience Grade 3 or 4 bleeding during therapy. | |
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Do you feel that bevacizumab works better in combination with certain chemotherapy regimens (for example, taxanes)? | |
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The E4599 trial used carboplatin-paclitaxel chemotherapy and the AVAiL trial gemcitabine-cisplatin. Both trials attained the primary endpoint (Sandler AB et al. N Engl J Med. 2006:355:2542-2550; Reck M et al. |
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What specific cautions would you take when treating a hypertensive patient with NSCLC? | |
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Pre-existing hypertension should be adequately controlled before starting bevacizumab treatment. Bevacizumab is associated with hypertension, and therefore blood pressure monitoring should be conducted every 2-3 weeks during treatment. If bevacizumab has induced new or exacerbated hypertension, the blood pressure should continue to be monitored despite stopping bevacizumab. Hypertension is generally adequately controlled with oral antihypertensives, such as angiotensin-converting enzyme inhibitors, diuretics, and calcium-channel blockers. The use of diuretics to manage hypertension is not advised in patients who receive a cisplatin-based chemotherapy. Hypertension rarely resulted in discontinuation of bevacizumab treatment or hospitalisation. Bevacizumab should be permanently discontinued in patients with hypertensive crisis or hypertensive encephalopathy, and temporarily suspended in patients with severe hypertension that is not controlled with medical management. Interestingly, in a recent unplanned analysis of the E4599 trial, hypertension was associated with a somewhat better survival, although this observation needs to be confirmed in other studies (Dahlberg S et al. J Clin Oncol. 2010;20:949-954). |
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| This activity is supported by an unrestricted educational grant from F. Hoffmann-La Roche Ltd. |
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