The concept of maintenance therapy for advanced lung cancer has emerged over the past few years. Dr. Jack West, medical oncologist, reviews the concepts behind it and treatment options for patients.
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One of the core ideas in treating advanced non-small cell lung cancer is that we try to treat is aggressively, early on, to induce the greatest shrinkage we can, which tends to be associated with a longer survival for patients. This specifically means that we typically treat with a two, or sometimes three-drug combination as first-line therapy, and most of the time, when we see tumor shrinkage, it tends to be front-loaded, and we see that early on, in the first one or two scans done. Most commonly, we’ll give four to six cycles of treatment for patients with this multi-drug combination, and then think about stopping treatment or downshifting. This idea of downshifting to a less intensive therapy, but still keeping something going, is the idea of maintenance therapy.
So what is maintenance? It is essentially to maintain the tumor shrinkage that we achieved early on, with first-line therapy, but by using a more tolerable, less intensive regimen after that, that can be continued longitudinally, without too many cumulative side effects.
There are two main ways of approaching this — one is by doing what’s called continuation maintenance. You start with a two-drug or three-drug combination, and then you drop one or two of the agents off, and keep some of the first-line therapy going, but not all of it, and this makes it less intensive, and potentially able to be given for a much longer period of time to maintain the response that was achieved early on. An alternative approach is called switch maintenance, and that is starting with four to six cycles of a combination, then stopping all of those agents and switching to one or more agents after that, that have not been given before. Again, the idea is to come up with a regimen that is not too intensive, but that can maintain the momentum that was already achieved — basically keeping the tumor shrunk for longer.
Now, what do we hope to achieve by maintenance therapy? Several studies have demonstrated that there is a very consistent improvement in progression-free survival, the time before the cancer will progress, in patients who receive effective maintenance therapy. In just about all of the cases of what we call effective maintenance therapy, this is a treatment that is essentially a standard second-line treatment, but we give it earlier than second-line, which is when the patient has actually demonstrated progression of their cancer; instead, we’re giving it more proactively — immediately after first-line, and these agents that have been shown to improve survival when given second-line, after progression, are also associated with improvement in progression-free survival, and in some cases, significant improvement in overall survival when given earlier on, as a maintenance therapy.
However, there are some potential issues and questions about how necessary maintenance therapy really is, and although it is certainly a widely practiced approach and a standard of care, it is not a mandate at this point. This is because — the fact is that, the studies that give maintenance therapy do have an imbalance, where more of the patients on randomized maintenance therapy received more intensive therapy than the patients who are randomized to receive supportive care, or no treatment, just placebo perhaps, instead, at the time of completing first-line therapy. So, what we actually see is, sometimes it may just be that more treatment is associated with better outcomes, and longer survival, than less treatment. But, one thing we can say is that maintenance therapy assures us that the patients who have achieved tumor shrinkage, or at least stable disease, and are therefore the patients most likely to benefit from later treatment, definitely get that later therapy that can help them.
One of the challenges and issues about taking breaks from treatment is that some patients will decline and not be well enough to receive additional treatment that would have otherwise helped them if they had just gotten it earlier. So, with some patients potentially falling off the curve, missing that opportunity, there is a tendency to try to push effective treatment to earlier, and minimize time off of therapy where we might have patients miss that opportunity if they decline quickly.
So, that is the general approach to maintenance therapy — it is not a mandate, but it is something that we tend to individualize for our patients, and discuss whether they feel up to tolerating more treatment after going through four to six cycles of a combination first-line therapy, and whether they need to have a break, whether they want to go on a family vacation, etc.; there’s always room for individualizing, but for many patients, continuing with maintenance therapy — either continuation, or sometimes switch maintenance to a new therapy, may be a very appropriate approach.