Considerations When Deciding on a Lung Cancer Treatment
Edward S. Kim, MD: There are a lot of considerations that still go into seeing if you’re going to be a candidate to have the third drug, Avastin, added to your doublet. Again, there are many choices out there, so don’t think it’s a wrong choice or right choice if you do or don’t. The doctors are going to think about several things. Again, I mentioned fitness. You’ve got to be in pretty good shape.
There are also different characteristics that will be considered that are related to side effects. But mostly, it’s going to be, what is the appropriate therapy? There are a lot of them out there—2-drug regimens. A popular one is carboplatin and paclitaxel (Taxol). That was the most popular regimen in the early 2000s, and that’s the backbone that added Avastin and showed a benefit in survival. There have also been other regimens approved, including a drug called pemetrexed (Alimta). And that, too, is a very popular regimen when you combine it with carboplatin in patients who don’t have driver mutations that will direct therapy. There are some folks out there who will actually combine Avastin with carboplatin and Alimta, and there can be some benefit there as well.
So, to summarize, there’s many choices. There are several doublets. I’m not saying this to confuse you. It’s the reality of the treatment in lung cancer right now with chemotherapy. There should be consideration, always, to add a third drug in the appropriate clinical setting with a doublet.
Mark A. Socinski, MD: The use of antiangiogenic agents is somewhat restricted to a certain patient type in the first-line setting, so a first-line treatment would include the option of bevacizumab. Bevacizumab is a drug that’s contraindicated in patients who have squamous histology, so it’s important to know that.
There are a number of relative contraindications. For instance, recent heart attacks, recent strokes, recent blood clots, those sorts of things. There’s also an issue of age in that the older you are, and I’m talking about over 75, 80, the potential risk of side effects with bevacizumab seems to go up. So, I think that in the extreme elderly, you need to think seriously about whether or not that’s the right thing to do for the patient. The reason we consider doing it is because when you add it to chemotherapy, it has been demonstrated to improve longevity, to help shrink cancers more often, and to control those cancers better for a longer period of time. So, it can be potentially helpful. But like everything in life, you must balance the risk and the benefit in each individual case.
Edward S. Kim, MD: The data that came out when combining Avastin with chemotherapy was beneficial and really changed practice patterns. It made folks realize that you could add a third drug and there would be some benefits. Some of the benefits that were demonstrated in the study included shrinking the tumors at a higher rate—35% versus 20%. Also, the survival of patients increased by over 2 months. Some people say, “Well, gosh, 2 months isn’t that much.” Well, just remember, earlier I talked about other studies that tried to add a third drug and no benefit was shown whatsoever. So this was the first time that a third drug showed survival. And 2 months was a big deal to us, especially in a nondriver mutation setting. So there can be side effects. We watch for things. We watch your kidneys, we watch your blood pressure. Some patients will complain they’ll get a few nosebleeds every now and then, but we try to be cautious about, again, who we give the drug to. For the most part, many patients can receive this drug and it is very well tolerated.
Mark A. Socinski, MD: Bevacizumab is a well-tolerated drug in the majority of patients. One has to exercise a good patient selection. There are clearly reasons, or patients, in which I would not use it. But if you judge correctly and select patients correctly, it’s actually one of the better tolerated drugs that I use. The typical side effects we see are blood pressure issues and muscle aches and pains. It can cause your kidneys to leak a little bit of protein, so that has to be monitored. Some other rare complications of bevacizumab include pulmonary hemorrhage, and gastrointestinal perforation has been described. Other complications are exceedingly rare and so uncommon that they don’t generally factor into my decision to recommend it or not.
There’s always a concern with a patient on bevacizumab with regard to wound healing. You can’t predict the future. Sometimes patients need surgery for some other problem; they may need their gallbladder out. I worry about those patients in wound healing. But there’s no way to predict that that’s going to happen or not. Certainly, if I knew that a patient needed to have surgery for some reason that I would like, I would probably hold the bevacizumab for 6 to 9 weeks prior to the surgical procedure (if it’s elective). It’s not always elective. But if I knew about it ahead, I would hold the bevacizumab because of the wound-healing complications.