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GRACE Video

Maintenance Therapy for Advanced NSCLC

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GRACEcast-522_Lung_West_Maintenance_Therapy_Advanced_NSCLC

 

Dr. Jack West, Swedish Cancer Institute, defines maintenance therapy in advanced NSCLC and discusses maintenance treatment strategies.

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For patients with advanced non-small cell lung cancer, our typical approach, if we have someone who does not have a driver mutation that we typically treat with a pill-based targeted therapy, is to give chemotherapy. That chemotherapy is typically given in a cycle of three weeks or sometimes a four week period of time where the blood counts go down and then recover. That treatment is typically given once every three weeks, sometimes once or twice on a weekly basis in that three week interval, but we typically give that therapy for about four to six cycles of therapy — that’s about three to five months of treatment. By that time, by four to six cycles in, the two drug combination that includes a drug called platinum is usually creating some cumulative side effects: fatigue, low blood counts, and other complicating issues that make it increasingly challenging to administer more of the same potentially intensive therapy, and by four to six cycles you really tend to reach a point of diminishing returns.

At that point we often favor a maintenance therapy approach. That is, dropping the carboplatin or stopping all of the agents that have been given previously and either continuing one or more of the agents from the first line setting, or using what’s called switch maintenance to give a completely different treatment. These maintenance therapies are designed to do what their name suggests — to maintain a response after we’ve seen the most shrinkage that we’re likely to get from the more intensive first line therapy.

When we do a continuous maintenance approach, it’s typically taking a drug like cisplatin or carboplatin in combination with one or two partner drugs, usually a second chemotherapy agent and sometimes Avastin which blocks a tumor’s blood supply, and then after four to six cycles we drop the platinum and we will typically continue a drug like Alimta if that’s been given in the first line setting, and if a drug like Avastin has also been given we might continue that and give Alimta and Avastin together until the cancer progresses.

If a combination like carboplatin and Taxol were given with Avastin, the maintenance therapy is often just the Avastin because Taxol tends to have some cumulative neuropathy issues — numbness and tingling that can lead to a real limitation in how much of that therapy you can give. We might also consider a switch maintenance approach — instead of continuing some of the agents, come in with Alimta as a single agent if a patient has non-squamous histology. Another agent that is approved as a switch maintenance therapy is Tarceva (erlotinib) — this doesn’t tend to be as favored as a switch maintenance because the efficacy of Tarceva in patients who don’t have an EGFR mutation tends to be on the lower side.

What do these maintenance therapies have in common? Well they’re all agents that can be given on a longitudinal basis without a lot of cumulative side effects and they tend to be the agents that have good activity in patients who have already been on prior therapy. So any of these is a reasonable choice, the most common being a continuation maintenance of dropping the platinum and continuing one or two partner drugs that were given with it, or sometimes switching to an agent like Alimta (pemetrexed) or Tarceva (erlotinib). It’s also reasonable to not pursue maintenance therapy if a patient has cumulative side effects and really needs a break from therapy. That is certainly something to discuss with the patient; it’s not as if maintenance therapy is a mandate for all patients, but it is something that is a strong consideration if a patient is motivated and can continue to tolerate ongoing therapy after four to six cycles.


GRACE Video

What is Maintenance Therapy for Advanced NSCLC?

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GRACE Cancer Video Library - Lung

GCVL_LU-F11_Maintenance_Therapy_Advanced_NSCLC

 

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.

GCVL_LU-F11_Maintenance_Therapy_Advanced_NSCLC.001

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.


Dr West

What is the value of maintenance therapy in advanced NSCLC, and who should get it?

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We’ve covered the question of maintenance therapy for lung cancer in many posts over the past 5-6 years as it has evolved from a concept with little evidence to a standard of care, but it is difficult to get a good summary of the big picture. This presentation is my attempt to distill the field into the most important principles.

 

What is the value of maintenance therapy in advanced NSCLC, and who should get it? from H. Jack West

And for those who want to download the slides in an easily printable form, here’s the slide set as a pdf file: Maintenance therapy primer

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GRACE Video

Dr. Rosalyn Juergens on “My Approach to Maintenance Therapy for Advanced NSCLC”

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Dr. Rosalyn Juergens, McMaster University, discusses the evidence and her personal interpretation and recommended approach to maintenance therapy for advanced non-small cell lung cancer.


GRACE Video

Dr. Heather Wakelee on “My Approach to Maintenance Therapy for Advanced NSCLC”

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Dr. Heather Wakelee, from Stanford University, discusses the evidence and her personal interpretation and recommended approach to maintenance therapy for advanced non-small cell lung cancer.


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