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Maintenance Strategies in Lung Cancer

Panelists: Gerald J. Berry, MD, Stanford University; David Spigel, MD, Sarah Cannon Research Institute; Heather Wakelee, MD, Stanford University; Anne S. Tsao, MD, MD Anderson Cancer Center
Published: Monday, Jul 10, 2017


Transcript:

Anne S. Tsao, MD:
In nonsquamous non–small cell lung cancer, we do like to consider maintenance treatment, especially if patients don’t have a driver mutation and are getting systemic chemotherapy. If they’re getting platinum pemetrexed, then usually after 4 to 6 cycles, in patients with stable disease who are responsive, I like to give maintenance pemetrexed. In patients where we add the bevacizumab to their initial therapy, we do consider either continuing pemetrexed maintenance or doing pemetrexed/bevacizumab maintenance. I think any patient who has a good performance status, who is tolerating therapy very well, and who has a stable disease or response should be considered for, or offered, the option of stimulant maintenance treatment.

Heather Wakelee, MD: We have different platinum doublets to choose from for our patients with metastatic lung cancer. Those include carboplatin or sometimes cisplatin, and then we can couplet with different drugs. The one used most often in adenocarcinoma is pemetrexed, and there are randomized phase III data supporting maintenance pemetrexed if that drug is given.

So, patients who get 4 to 6 cycles of carboplatin and pemetrexed or cisplatin and pemetrexed—if they continue on pemetrexed as a single agent afterward—have a longer progression-free survival and overall survival compared to stopping it and not giving a maintenance therapy. That is the way that the drug is routinely given.

We still have some questions around maintenance, and one of those has to do with if we’re adding in bevacizumab, the anti-VEGF antibody. If that drug is given with the carboplatin/paclitaxel, which is how it was studied on the ECOG 4599 trial, then the carboplatin/paclitaxel is stopped after 4 to 6 cycles and the bevacizumab is continued. Do we know that we have to do that? We don’t.

There is an ongoing ECOG trial where patients received the carboplatin/paclitaxel and bevacizumab after the 4 cycles. Those who had not progressed were then randomized to get bevacizumab alone, which is the same as the ECOG 4599 regimen, or to get the chemotherapy drug pemetrexed or to get both. So, that’s going to give us some more information about what the role of maintenance with bevacizumab is, what the role of maintenance with pemetrexed is in a switch maintenance setting, what the role of both is, and if there is an advantage to combining those drugs together.

We don’t have the data yet to know if that’s the way things are going to move or not and which of those drugs will be the standard. But the standard of care at this time is that if bevacizumab is given, it’s given as maintenance; if pemetrexed is given, it’s given as maintenance. Sometimes the two are given together as maintenance, but we don’t have firm data about that yet to say that it’s the right way to go.

When patients are given other platinum doublets like paclitaxel, they’re not usually continued because of ongoing issues with neuropathy. There is a study looking at patients who are getting nab-paclitaxel, where that drug may be able to be continued as the maintenance, but that’s an ongoing trial. Gemcitabine is sometimes given as maintenance, if it’s given as part of a platinum doublet. The data there are a little bit softer. I do tend to do that in my patients to whom I give gemcitabine, but a lot of other people don’t. So, that is how we think about maintenance.

If I give platinum pemetrexed, I always give pemetrexed maintenance. Usually, it’s well-tolerated. Usually, over time, we do have to lower the dose, we do have to spread out the treatment interval. And we tend to do that stepwise so that if patients are on for a year—and many of them are—they’re usually getting it at a lower dose every 4 weeks as opposed to the initial dosing every 3 weeks.

Occasionally, patients will start to develop more issues with fatigue over time, which necessitates those reductions and even stopping the therapy. Sometimes, more edema will build up over time and then we’ll have to stop. There are reasons that things can happen—renal function issues—where we have to stop, but the vast majority of patients do tend to be able to tolerate the maintenance as long as the drug is still controlling the cancer.

Anne S. Tsao, MD: Maintenance pemetrexed is actually a good option for many of our patients. We know that it improves progression-free and overall survival and is very well tolerated. The main side effects that you do want to watch out for are anemia and, certainly, the patients getting fatigued. Those are always important to monitor. It’s important to make sure the patients are taking their vitamin supplementation, maintaining their weight with a good diet, and taking the dexamethasone premedication. If they do that, then you can also maintain them with maintenance pemetrexed for quite some time.

David Spigel, MD: Pemetrexed is a drug that I use as a maintenance therapy. I think that early in its development, we were giving 4 cycles alone. But we know from pivotal randomized trials that maintenance therapy in different settings can be valuable. This is true in pemetrexed. When you give somebody 4 cycles of a platinum doublet that includes pemetrexed and then you continue pemetrexed alone, compared with patients who just stop therapy at that point, there’s an improvement in overall survival in the group that continues pemetrexed. That’s my strategy. I give pemetrexed as long as patients are tolerating it and are benefitting from it. So, if there’s no progressive disease, I believe that they can benefit in terms of long-term disease control and overall survival.

Most of the patients I offer maintenance pemetrexed to choose to remain on it indefinitely. But there can be patients who simply don’t want to do that. They would prefer to stop or take what we call holidays, where they take a month, or 2, or 3, off. I even do some unusual things sometimes where, instead of every 3 weeks, I’ll agree to an alternate schedule, say every month, or I’ll even stretch that a little bit longer for patients.

But, in general, maintenance therapy is something that I’ve become a supporter of. But I only do it with pemetrexed. I don’t do that with other chemotherapeutic agents. I do use bevacizumab, although I don’t use much as I used to. That is another drug I use in a so-called maintenance fashion. But, by and large, pemetrexed is the maintenance drug I use.

Transcript Edited for Clarity
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Transcript:

Anne S. Tsao, MD:
In nonsquamous non–small cell lung cancer, we do like to consider maintenance treatment, especially if patients don’t have a driver mutation and are getting systemic chemotherapy. If they’re getting platinum pemetrexed, then usually after 4 to 6 cycles, in patients with stable disease who are responsive, I like to give maintenance pemetrexed. In patients where we add the bevacizumab to their initial therapy, we do consider either continuing pemetrexed maintenance or doing pemetrexed/bevacizumab maintenance. I think any patient who has a good performance status, who is tolerating therapy very well, and who has a stable disease or response should be considered for, or offered, the option of stimulant maintenance treatment.

Heather Wakelee, MD: We have different platinum doublets to choose from for our patients with metastatic lung cancer. Those include carboplatin or sometimes cisplatin, and then we can couplet with different drugs. The one used most often in adenocarcinoma is pemetrexed, and there are randomized phase III data supporting maintenance pemetrexed if that drug is given.

So, patients who get 4 to 6 cycles of carboplatin and pemetrexed or cisplatin and pemetrexed—if they continue on pemetrexed as a single agent afterward—have a longer progression-free survival and overall survival compared to stopping it and not giving a maintenance therapy. That is the way that the drug is routinely given.

We still have some questions around maintenance, and one of those has to do with if we’re adding in bevacizumab, the anti-VEGF antibody. If that drug is given with the carboplatin/paclitaxel, which is how it was studied on the ECOG 4599 trial, then the carboplatin/paclitaxel is stopped after 4 to 6 cycles and the bevacizumab is continued. Do we know that we have to do that? We don’t.

There is an ongoing ECOG trial where patients received the carboplatin/paclitaxel and bevacizumab after the 4 cycles. Those who had not progressed were then randomized to get bevacizumab alone, which is the same as the ECOG 4599 regimen, or to get the chemotherapy drug pemetrexed or to get both. So, that’s going to give us some more information about what the role of maintenance with bevacizumab is, what the role of maintenance with pemetrexed is in a switch maintenance setting, what the role of both is, and if there is an advantage to combining those drugs together.

We don’t have the data yet to know if that’s the way things are going to move or not and which of those drugs will be the standard. But the standard of care at this time is that if bevacizumab is given, it’s given as maintenance; if pemetrexed is given, it’s given as maintenance. Sometimes the two are given together as maintenance, but we don’t have firm data about that yet to say that it’s the right way to go.

When patients are given other platinum doublets like paclitaxel, they’re not usually continued because of ongoing issues with neuropathy. There is a study looking at patients who are getting nab-paclitaxel, where that drug may be able to be continued as the maintenance, but that’s an ongoing trial. Gemcitabine is sometimes given as maintenance, if it’s given as part of a platinum doublet. The data there are a little bit softer. I do tend to do that in my patients to whom I give gemcitabine, but a lot of other people don’t. So, that is how we think about maintenance.

If I give platinum pemetrexed, I always give pemetrexed maintenance. Usually, it’s well-tolerated. Usually, over time, we do have to lower the dose, we do have to spread out the treatment interval. And we tend to do that stepwise so that if patients are on for a year—and many of them are—they’re usually getting it at a lower dose every 4 weeks as opposed to the initial dosing every 3 weeks.

Occasionally, patients will start to develop more issues with fatigue over time, which necessitates those reductions and even stopping the therapy. Sometimes, more edema will build up over time and then we’ll have to stop. There are reasons that things can happen—renal function issues—where we have to stop, but the vast majority of patients do tend to be able to tolerate the maintenance as long as the drug is still controlling the cancer.

Anne S. Tsao, MD: Maintenance pemetrexed is actually a good option for many of our patients. We know that it improves progression-free and overall survival and is very well tolerated. The main side effects that you do want to watch out for are anemia and, certainly, the patients getting fatigued. Those are always important to monitor. It’s important to make sure the patients are taking their vitamin supplementation, maintaining their weight with a good diet, and taking the dexamethasone premedication. If they do that, then you can also maintain them with maintenance pemetrexed for quite some time.

David Spigel, MD: Pemetrexed is a drug that I use as a maintenance therapy. I think that early in its development, we were giving 4 cycles alone. But we know from pivotal randomized trials that maintenance therapy in different settings can be valuable. This is true in pemetrexed. When you give somebody 4 cycles of a platinum doublet that includes pemetrexed and then you continue pemetrexed alone, compared with patients who just stop therapy at that point, there’s an improvement in overall survival in the group that continues pemetrexed. That’s my strategy. I give pemetrexed as long as patients are tolerating it and are benefitting from it. So, if there’s no progressive disease, I believe that they can benefit in terms of long-term disease control and overall survival.

Most of the patients I offer maintenance pemetrexed to choose to remain on it indefinitely. But there can be patients who simply don’t want to do that. They would prefer to stop or take what we call holidays, where they take a month, or 2, or 3, off. I even do some unusual things sometimes where, instead of every 3 weeks, I’ll agree to an alternate schedule, say every month, or I’ll even stretch that a little bit longer for patients.

But, in general, maintenance therapy is something that I’ve become a supporter of. But I only do it with pemetrexed. I don’t do that with other chemotherapeutic agents. I do use bevacizumab, although I don’t use much as I used to. That is another drug I use in a so-called maintenance fashion. But, by and large, pemetrexed is the maintenance drug I use.

Transcript Edited for Clarity
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