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What is the Role of Bevacizumab in Stage IV NSCLC?
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Dr. Jack West, Swedish Cancer Institute, discusses the anti-angiogenic agent bevacizumab (Avastin) and the trial evidence of its efficacy for non-squamous NSCLC.




In addition to standard chemotherapy, usually a two drug combination, we sometimes add a third drug called Avastin, also known as bevacizumab. Now this is not a standard chemotherapy agent — instead Avastin acts as an anti-angiogenic therapy, that is, it blocks the tumor’s blood supply, and it is sometimes included in the treatment regimen really only for the patients who have a non-squamous cancer.

Why is that? Well, years ago when Avastin was first being studied in many different kinds of patients with lung cancer — non-small cell lung cancer, either squamous or non-squamous, we found that a significant minority of patients had problems with bleeding complications, specifically coughing up blood that reached a potentially life-threatening or fatal level. That was found to be almost always limited to the patients with squamous histology. So obviously we decided that was not the way to go, and studies after that really limited treatment with Avastin to patients with non-squamous lung cancer. After that we found that even though you could have bleeding complications in a small minority of patients, it was much less of a concern when Avastin is limited to patients with non-squamous lung cancer.

Now, it is FDA approved in combination with two-drug chemotherapy, specifically the combination of carboplatin and Taxol, also known as paclitaxel. That’s because a key trial known as ECOG 4599, which was done across many different centers in North America, compared standard chemotherapy with carboplatin and paclitaxel or Taxol, to the same chemotherapy with Avastin added to it. The study found that patients tended to live longer by an average of about two months. Because of that, and the tolerable side effect profile, it became standard of care to at least consider adding Avastin to the two-drug chemotherapy combination for patients with non-squamous histology.

Now importantly, a couple of other studies have been done since that time, also using Avastin, that didn’t clearly show a survival benefit, and because of that, Avastin is really considered an option but not an absolute mandate, and many oncologists do not routinely use it for most or all of their patients. It’s something to discuss with a patient perhaps, but for patients who have a history of brain metastases or any potential bleeding complications, it may not be advisable because the safety may be enough of a concern to minimize that, and it has not consistently shown a survival benefit after that ECOG trial that I mentioned. But, for some patients it is reasonable to do a two-drug combination of chemotherapy, whether that is carboplatin and Taxol, or perhaps a different one such as carboplatin and Alimta, also known as pemetrexed, while adding Avastin to that.

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