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Zoledronate or Denosumab for Lung Cancer with Bone Metastases

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GCVL_LU-CB04_Zoledronate_Denosumab_LC_Bone_Metastases

 

Dr. Benjamin Levy, Mount Sinai Health Systems, compares zoledronic acid and denosumab, two agents used for treatment of bone metastases in lung cancer.

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One of the important points about patients with advanced lung cancer is that 30-40% of patients will develop bone metastases. I think it’s important to recognize this is not bone cancer, this is lung cancer that’s moved to the bone, and in 30-40% of patients at some point who have advanced stage lung cancer, they will develop bone metastases. The question is: how do you manage these patients?

Now of course they’re going to be treated with chemotherapy or targeted therapies or immunotherapies to help control the cancer, but one of the other strategies that’s employed are bone strengthening agents. They come in really two forms, and the goals of giving a bone strengthening agent really are to delay skeletal-related events or fractures, and also strengthen the bones. I would say that they’re the standard of care for any patient with lung cancer who has bone metastases.

So currently there are two approved drugs for lung cancer patients with bone metastases. The first is called zoledronic acid, it’s given every three weeks and it’s a class of drugs called a bisphosphonate. These drugs are also used for osteoporosis. What we know about zoledronic acid or Zometa is that it does delay skeletal-related events or fractures in patients who get these drugs who have bone metastases in lung cancer.

The second class of drugs are called RANK-Ligand inhibitors, and the drug that’s approved for lung cancer is denosumab or Xgeva. This drug is a little different in its administration — it’s given subcutaneously rather than intravenously, and it’s also given every four weeks rather than every three weeks.

I think what we know about both of these drugs is that they do help strengthen the bones and delay skeletal-related events, but there’s a hint that denosumab, that second drug I mentioned, may also have some sort of anti-tumor effect. I’m not sure that this is completely ironed out in the literature, but we do know at least in one study published in 2012 that patients who actually got denosumab as a bone strengthening agent actually lived longer than those patients who got zoledronic acid. Now whether we can make or glean any major messages from this, I’m not sure. Nevertheless, my practice has been that any patient with lung cancer who develops bone metastases needs to be put on one of these two drugs.

These drugs do have side effects — one of the side effects with zoledronic acid is osteonecrosis of the jaw. This has happened in a very, very small percentage of patients so I don’t think that’s enough of a concern for me not to use the drug. Both of these drugs are extremely well tolerated and actually do help with the end points that I mentioned in terms of delaying fracture for those patients with bone metastases, but also potentially improving outcomes specifically with denosumab.


GRACE Video

How Rate of Progression Can Affect Treatment Decisions

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GCVL_LU-F03_Progression_Rate_Affect_Treatment_Decisions

 

Dr. Benjamin Levy, Mount Sinai Health Systems, explains how the rate of progression of a patient’s cancer may affect treatment choices.

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I think we know a lot now about how to treat patients with advanced stage lung cancer, and there are several things that we factor in when we treat patients. One is clearly the genetic makeup of their tumor — we tend to look at this when we’re trying to decide on a targeted drug for these patients. The other is perhaps histology, looking at a particular type of lung cancer whether it be adenocarcinoma or squamous cell, and deciding what type of chemotherapy we’re going to give. One that I would also like to mention that’s sometimes factored into treatment decisions is the variability of the aggressiveness of the tumor, meaning that some lung cancers can be very aggressive, and despite popular belief, some can be quite indolent.

Now while most lung cancers are thought to be more aggressive, I have come across many patients with lung cancers that tend to grow less rapidly, and the thought is: how do we factor this in when we’re making treatment decisions? I think the variability of progression plays out in two clinical scenarios.

One is a patient who is on chemotherapy or even on a targeted drug who’s doing well and tolerating the drug, and in which we are ordering scans every six to twelve weeks and we’re seeing that the tumor is growing but at a very limited pace, and the question is: if the patient is tolerating the chemotherapy or the targeted drug, should that limited pace of growth trigger a treatment change? I would say in our practice, not necessarily. Sometimes if growth is small, or growth is limited, or the pace is limited, sometimes we will keep patients on that particular therapy. My thought is they’re probably deriving some sort of benefit from that therapy if they’re tolerating it.

I think the other scenario where this plays out is for a patient who perhaps hasn’t been tolerating therapy and is on a treatment break. Sometimes not all patients tolerate chemotherapy and may need a treatment break, particularly when they get to maintenance, and the question becomes: if the cancer is growing on scans while they’re on a treatment break, should you reinstitute the drug or even reinstitute another drug? Again, I think that depends on how quickly things are moving along — for patients who may have not tolerated treatment well who are on a treatment break and their cancer is growing very, very slowly, I think it’s reasonable to continue to watch them as long as they understand that the cancer may grow rapidly at some point.

So I think these are important considerations when you’re treating a patient, not only to look at the genetic alterations in the tumor, not only to look at histology, but also to consider the natural evolution of this cancer and how it’s moving, and how quickly it’s growing when making treatment decisions.


GRACE Video

Platinum-Based Doublets As the Cornerstone of First Line Treatment

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GCVL_LU-F02_Platinum_Doublets_First_Line_Treatment

 

Dr. Benjamin Levy, Mount Sinai Health Systems, discusses platinum-based chemotherapy as the standard of care for advanced NSCLC patients without targetable genetic mutations.

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I’m going to be talking about the role of platinum chemotherapy for patients with advanced stage non-small cell lung cancer. No doubt, there have been significant advances in the past ten years with the development of targeted drugs for those patients who have a particular genetic makeup of their tumor. Many of these drugs have shown to be quite effective for those patients that are susceptible to such treatments. I think what we know though is unfortunately many patients will not have the genetic alterations that make them eligible for targeted treatments, and we have to default to chemotherapy.

I think ‘default’ is a bit of a misnomer because platinum chemotherapy or platinum doublet chemotherapy remains a standard of care for patients with advanced stage lung cancer who don’t harbor particular genetic alterations in their lung cancer and that’s okay. I think what we know about chemotherapy, platinum chemotherapy specifically, is that this type of approach improves survival for patients and it also can have the potential to improve quality of life as well as control symptoms as they relate to the lung cancer. So all three of those measures can be achieved with platinum chemotherapy.

Now chemotherapy comes in a variety of different shapes and sizes — the chemotherapy that we tend to use sometimes is called histology-directed chemotherapy, so patients with a particular type of lung cancer called adenocarcinoma may get one type of platinum chemotherapy, whereas patients with a particular type of lung cancer called squamous cell may get a different type of chemotherapy.

I just want to speak briefly about maintenance chemotherapy for adenocarcinoma patients. This is the most common type of lung cancer we see, and again for those patients that don’t harbor genetic alterations that make them eligible for targeted drugs, we can offer a very effective chemotherapy that’s also very tolerable and that can also be given as a maintenance strategy. What I mean by that is that patients generally get four cycles of chemotherapy and for those patients that at least achieve stable disease after their four cycles and are tolerating treatment, I think that we have good data now that we can drop the platinum and continue one of the drugs called pemetrexed and provide a survival advantage for those patients. There are certain maintenance strategies that are also being looked at in the squamous cell population and there are studies ongoing for that.

I think, in some, that the chemotherapies we have now work very well, they can extend life, they can improve quality of life and they’re well tolerated, and I also think specifically for the subset of patients that come in with adenocarcinoma or non-squamous, that there should be a consideration for patients who are tolerating chemotherapy to be offered a maintenance approach.


GRACE Video

What are the Goals of Treating Advanced NSCLC?

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GCVL_LU-F01_Goals_Treating_Advanced_NSCLC

 

Dr. Benjamin Levy, Mount Sinai Health Systems, lists the goals of treating advanced NSCLC and the methods used to achieve those goals.

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I think there are several goals when treating a patient with advanced non-small cell lung cancer. For one I think we want to extend life, two is I think we want to palliate symptoms, and three is I think we want to improve quality of life. So all three of those goals are achievable, I think, with the therapies that we have right now.

Now, some of these therapies are targeted drugs, so for patients that have genetic alterations or a genetic makeup that makes them eligible for targeted drugs, then clearly we can offer these drugs and I think we can achieve all three of those goals. But even for patients without genetic alterations, and patients who will not be receiving targeted drugs, I think we can extend life, improve quality of life and palliate symptoms by delivering chemotherapy. I think we know now that chemotherapy is not the chemotherapy of the days of old — these drugs are given in combination, are tolerable and can improve outcomes. We also have now immunotherapy, and so all three types of systemic approaches can help achieve these three goals.

In addition to these three goals, I think it’s important that we also have goals of care discussions with patients from the being of treatment. I think what that means is that we really come up with what the shared expectations are for treatment. Patients may ask specific questions like “how many months will additional chemotherapy give me versus no chemotherapy?” I think these questions are fair game. I think we can certainly talk about averages but also tell patients that they’re not an average and I would sway doctors or patients receiving information not to stick to exact numbers, but I do think that a goals of care discussion upfront is very important.

That brings into the realm the role of palliative approaches or palliative care. Many patients feel that palliative care is hospice or end of life care, but this is not the case. I think what we know now is that patients who have early palliative care referrals to palliative care specialists in conjunction with their treatment, specifically for lung cancer patients, these patients actually live longer.

So I bring up this whole concept of discussing goals of care very early on so we can make sure that our patients are referred to palliative care specialists who can treat patents alongside us and work in conjunction to help improve outcomes for our patients.


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