Tag Archive for: CDK4-6 inhibitors

Understanding Small Cell Lung Cancer Treatment Options

Understanding Small Cell Lung Cancer Treatment Options from Patient Empowerment Network on Vimeo.

How is small cell lung cancer (SCLC) treated? Dr. Triparna Sen discusses treatment options for patients with small cell lung cancer, both first-line and second-line therapies, and the important role of clinical trials in patient care. 

Dr. Triparna Sen is an associate professor in the department of oncological sciences and co-director of the Lung Cancer PDX Platform at the Icahn School of Medicine at Mount Sinai in New York. Learn more about Dr. Sen.

See More from Thrive Small Cell Lung Cancer

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Essential Small Cell Lung Cancer Testing

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Advances in Small Cell Lung Cancer Research | Hope for the Future

Transcript:

Katherine:

How do test results impact care? 

Dr. Sen:

So, you know, once the doctor has confirmed the small cell lung cancer and we have confirmed what stage it is at – what I mean by staging is that it could be either a limited stage disease which is an early stage small cell, or it could be an extensive stage of small cell. The treatment for those two are quite different. So, if it is an early stage or limited stage, patients are usually treated with chemoradiation. If it is an extensive stage or a metastatic small cell, then patients are usually given a standard of care which is chemotherapy in culmination with immunotherapy which is an antibody against PD-L1.  

Katherine:

You’re talking about treatment options that are currently available for small cell lung cancer. What about targeted therapies?  

Dr. Sen:

There aren’t very many therapeutic strategies that are targeted therapies as we speak like we hear from non-small cell lung cancer.  

So currently, like I mentioned, the frontline treatment for small cell lung cancer is with chemotherapy and immunotherapy and maintenance with immunotherapy alone.  

Once the patient relapses, which often is the case – all patients actually have resistance to the frontline chemo-io (chemoimmunotherapy) at some point in time. Once they have a relapse disease, the second line of therapy until now is with either topotecan or irinotecan which are two topoisomerase inhibitors or with lurbinectedin which is in the second line.  

So, when it comes to targeted therapies, so far we a have seen, you know, the conventional way that we think about EGFR inhibitors or KRAS inhibitors, it hasn’t been the case so far with small cell lung cancer. It’s very limited in the current approved setting. But there are many clinical trials that are investigating several targeted therapies that are either targeting – I can speak about that more as I talk about research strategy. But there are many targeted agents that are targeting surface targets like DLL3, B7-H3, or SEZ6. There are other targets that are targeting things like DNA damage repair, proteins, or epigenetic regulators like LSD1. But so far in the approved setting, it is quite limited.  

Katherine:

When we look at what therapies are available, what treatment options are available, what are some typical side effects? How are they managed?  

Dr. Sen:

Some of the major side effects that you see, especially with a frontline chemo-io (chemoimmunotherapy), are very common like you see with other cancer types. Also, it’s usually myelosuppression.  

I think it is prevented or is managed either by dose reduction or treatment delays or treated with transfusion. There has been research that CDK4/6 inhibitors, trilaciclib, when treated with in combination with chemotherapy can bring down the side effects that we see with chemotherapy.  

Some of the immunotherapy related adverse events includes pneumonitis, colitis. They are usually treated with early steroids, treatment withholding, and also it could be leading to permanent discontinuation of the treatment if the adverse events are really severe. Those are mainly what we see we the chemo-io (chemoimmunotherapy) regimen that is given up front.  

Katherine:

Okay. What questions should someone be asking about their proposed treatment plan?  

Dr. Sen:

Right. So, I think, of course, first is what stage. The treatment will depend upon the stage of small cell. Usually, on the frontline, everyone is given chemotherapy and immunotherapy. 

It’s a systemic therapy that’s being given. But I think the patient should be asking questions like are there clinical trials available for me. Because there are multiple clinical trials right now in the frontline and the second line setting.  

So, I think definitely the patient should ask about the clinical trials that the qualify for. In terms of contributing to research, I think if there are options for them to either sign up for blood collection protocol or for tissue collection protocol, I think the patient should definitely enroll for that.   

Because that really helps our research strategy. But in terms of treatment, I think they should ask about available clinical trials that they qualify for.  

Katherine:

Let’s turn to clinical trials then. Patient participation, of course, is essential to finding new and better treatments. What would you say to someone who’s hesitant to participate in a clinical trial?  

Dr. Sen:

Yes. I mean, that’s often the thing. We hear about these novel drugs. They’re in trial. For a disease that’s that aggressive, I think once there is a relapse, I think clinical trials could be a very good option for patients. These are novel drugs that have come out of very robust research that we do in the lab. They can often work quite a bit. So, I think, of course, talk to your physicians. Talk to them at length about whether you do qualify for it. But if there is a trial at the center that you’re getting treated at and if the doctor advises that, I think enrolling in a clinical trial could be a very good option for patients, especially in the aggressive setting where there are not many options available for patients.  

As I mentioned here, research is my true north. I mean, all my lab does is understanding the biology of small cell. It’s extremely essential that we actually try to get the knowledge of the patient tumor. So, if you have availability of contributing either in terms of tissue or blood to research, I think I would advise and encourage patients to definitely contribute to that. 

An Overview of Metastatic Breast Cancer Treatment Options

An Overview of Metastatic Breast Cancer Treatment Options from Patient Empowerment Network on Vimeo.

What metastatic breast cancer (MBC) treatment options are available? Dr. Jane Lowe Meisel provides an overview of MBC treatment approaches, including CDK4-6 inhibitors, tyrosine kinase inhibitors, PARP inhibitors, and immunotherapy.

Jane Lowe Meisel, MD is an Associate Professor of Hematology and Medical Oncology at Winship Cancer Institute at Emory University. Learn more about Dr. Meisel here.

See More From INSIST! Metastatic Breast Cancer

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Transcript:

Katherine:

Right.

Well, let’s talk about treatment options for advanced disease. Can you review the types of treatments available for metastatic breast cancer?

Dr. Meisel:

Absolutely. And what I’ll do is, I’ll give you a broad overview and then because there’s so much and this is such a rich environment, I mean, I give hour long lectures just about the treatment of metastatic triple-negative breast cancer to our fellows. So, there is so much meaty information here. But I’ll give an overview with some key buzzwords so then people can go look up things that matter more to them or interest them more. So, as I said, we start with thinking about, is this hormone receptor-positive or estrogen-positive breast cancer? Is this HER2-positive or is this triple-negative? And those factors really send us down different paths.

So, if someone is estrogen-positive, I had mentioned before the PALOMA and MONALEESA studies showing that CDK4-6 inhibitors, which is a class of drugs that the first one was approved in 2015 and then two others have been approved subsequently. So, relatively new drugs. But those drugs, which are pills, added to traditional anti-estrogen therapy which would be aromatase inhibitors or fulvestrant.

Are often great first line options for these patients. And people can do well for years on just that alone, with estrogen-positive metastatic breast cancer. On average, about two years before people progress and need something new. And then after that, there are lots of trials ongoing looking at different ways in which an estrogen-positive breast cancer might progress on that regimen and how do we target that. So that there are multiple other anti-estrogen options down the line that people can use in estrogen-positive breast cancer before they need to even think about going on to something like chemotherapy.

So, really lots and lots of options for those patients, but probably starting with a CDK4-6 inhibitor plus anti-estrogen combination. And then in HER2-positive breast cancer, typically the first line treatment would be what we call monoclonal antibodies directed at HER2. So, something like Herceptin and Perjeta, which you may have heard of. And often combined with chemotherapy. But again, this is one of those areas that is also very, I think the art of medicine is very important and patient dependent.

Some of these regimen depend a little bit on patient’s age and other medical problems and desires, whether to include chemotherapy along with that frontline anti-HER2 regimen. Or whether to think about something like anti-estrogen therapy if the patient is HER2-positive and estrogen-positive. And then there are a lot of other different things we’re also using in HER2-positive disease after patients progress on that initial therapy, so there are what we call, antibody drug conjugates, where a chemotherapy like drug is attached to an antibody that then brings the chemo to the HER2-positive cell and allows for chemotherapy penetration more directly.

And then a class of drugs called tyrosine kinase inhibitors, which are oral drugs that get directed at HER2. So, another really exciting area to treat and a place where we’ve seen so many advances. And then in triple-negative breast cancer, I’d mentioned that chemotherapy has really been the mainstay of treatment historically because there weren’t great targets. But recently we’ve seen that immunotherapy, along with chemotherapy drugs like Keytruda, which you may have heard of.

Or atezolizumab, which is Mesenteric, can be used along with chemo and patients that overexpress a molecule called, PDL1. And that can actually include not just how long patients spend on the first treatment, but how long they live. So, we’re seeing a lot of triple-negative patients being great candidates for immune-based regimens now. And then for patients who have inherited a BRCA gene mutation, which many of you may have heard of. That gene mutation can actually predispose a triple-negative patient to be more receptive to a class of drugs called PARP inhibitors.

So, drugs like Olaparib or Talazoparib are new drugs that’ve been approved in the last couple of years in triple-negative metastatic breast cancer for patients who carry a BRCA1 mutation or BRCA2 mutation. And then there are also antibody drug conjugates in triple-negative breast cancer as well. The Trodelvy that’s been approved and then of course others that are in clinical trials currently. So, as you can see, it’s complex. I mean, the treatment of metastatic breast cancer is complicated. And so, it’s important I think to really be able to have a dialogue with your provider about what they’re recommending for you and why.

And I think there are often lots of options. And so, as much as you can make your doctor aware of what matters to you in terms of what side effects are you most afraid of or would you like most to avoid, what dosing schedules would be idea for your schedule for the rest of your life. So that you can deal with taking kids to school or the job that you’re currently working on or whatever, I think helps your doctor help you come up with the right regimen for you.