Hope Unleashed: Advancing Therapies for Defiant Mutations in Lung Cancer
Hope Unleashed: Advancing Therapies for Defiant Mutations in Lung Cancer from Patient Empowerment Network on Vimeo.
What promising studies in lung cancer mutations are there that patients should know about? Expert Dr. Joshua Sabari from NYU Langone discusses common lung cancer mutations, incidence rates, promising and potential studies, and proactive patient advice.
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“…no matter what your lung cancer type is, no matter any clinical characteristic, you need next generation sequencing done, biomarker testing done, to identify these mutations. And even when we identify the mutation, I think as a group, as an academic community, we need to do more to study novel therapeutics and to better understand the biology of these mutations so that we can get better treatments to our patients.”
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Lisa Hatfield:
Dr. Sabari, can you speak to some of the more defiant mutations in lung cancer, and what promising studies are we looking at right now?
Dr. Joshua Sabari:
Yeah, so I think in lung cancer the most common mutations that we see are EGFR and KRAS. EGFR mutations are a quite broad range of alterations. The most common are in exon 19 deletion and exon 21. These are the location of the mutations. They make up about 80 percent to 85 percent. We have phenomenal treatments in the frontline setting, but most patients only remain on therapy for about two years before there is progression. So, we need to better understand resistance mechanisms, and we need to better understand the next generation of therapies that are available.
In contrast to EGFR, KRAS is equally as common. We see this in about 25 percent to 30 percent of the patient population. Unlike EGFR, KRAS is almost exclusively seen in people who’ve smoked in the past. And there are many different KRAS mutations or alleles. There’s KRAS G12C where we have two FDA-approved match targeted therapies in the second-line setting.
But we need better options, better opportunities for our patients in the frontline setting. And for KRAS, we’re not doing as well as we should, right? KRAS mutations, most people have about a 30 percent to 40 percent chance of responding to therapy. And the median time on treatment is in that six to seven month range. So this is a defiant mutation. It’s a mutation where we need to do better and we need to really develop the next generation of inhibitors for our patients.
So I guess the activation tip here is, again, no matter what your lung cancer type is, no matter any clinical characteristic, you need next generation sequencing done, biomarker testing done, to identify these mutations. And even when we identify the mutation, I think as a group, as an academic community, we need to do more to study novel therapeutics and to better understand the biology of these mutations so that we can get better treatments to our patients.
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When Should Lung Cancer Patients Receive Biomarker Testing?
When Should Lung Cancer Patients Receive Biomarker Testing? from Patient Empowerment Network on Vimeo.
Biomarker testing is vital for non-small cell lung cancer (NSCLC) patients, but when should it happen? Expert Dr. Joshua Sabari from NYU Langone discusses cancer cell mutations and ideal timing for biomarker testing for the best patient care.
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Lisa Hatfield:
And just from the patient perspective, does a patient need to be tested for these biomarkers throughout the course of their treatment, or is it done initially upon diagnosis or before second-line treatment?
Dr. Joshua Sabari:
Yeah, that’s a great question. You know, most mutations are clonal, meaning that they start in the original cancer cell and then the subsequent cells, daughter or son cells, also have that same mutation. So I would recommend doing next-generation sequencing up front in all patients. Now, some people have a specific mutation that we block with a targeted therapy. It could be pills. It could be an infusional targeted therapy. And that might change the sort of milieu or landscape of that mutational profile. So subsequently, after treatment, you may see acquired resistance or secondary mutations that will prevent the therapies from being effective. In those cases, I do recommend re-profiling.
So the most common example in lung cancer is the EGFR mutation, stands for epidermal growth factor receptor. We know that this mutation occurs in 20 to 25 percent of people diagnosed with non-small cell lung cancer. If you’re matched to a targeted therapy and don’t unfortunately have progression of disease, it may be very helpful to re-biopsy or re-sequence using both tissue and plasma to help us guide subsequent therapy. But if you do not have a targeted mutation and you’re treated with either chemotherapy and immunotherapy or immunotherapy alone, re-biopsy may not be as helpful in matching to further therapy.
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Understanding Non-Small Cell Lung Cancer: Types, Biomarkers, and Treatment Insights
Understanding Non-Small Cell Lung Cancer: Types, Biomarkers, and Treatment Insights from Patient Empowerment Network on Vimeo.
How can non-small cell lung cancer (NSCLC) patients be empowered when newly diagnosed? Expert Dr. Joshua Sabari from NYU Langone discusses what he shares about NSCLC incidence rates, histology, and biomarkers with patients and families.
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“…know what type of cancer you have, the histology. Whether it be adenocarcinoma or squamous cancer. And equally as important, know your biomarker, what mutation is driving your cancer and what PD-L1 expression your tumor harbors.”
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Transcript:
Lisa Hatfield:
Dr. Sabari, how do you explain non-small cell lung cancer to your patients and their care partners and families?
Dr. Joshua Sabari:
Yeah, so non-small cell lung cancer is a common cancer in the United States. It’s actually the third most common cancer. And really, you know, non-small cell lung cancer makes up multiple different histologies or types of cancer in the lung. The most common being adenocarcinoma, which is probably about 60 percent to 70 percent of non-small cell. We also hear about squamous cell cancer. And what this means is what is the original cell where the cancer arose? So adenocarcinomas occur in gland cells.
Whereas squamous cancers occur in cells such as the lining part of the lung. And it’s important to know what type of cancer you have because these are treated differently. And when you think about non-small cell lung cancer, we said there are many different ways that people can present. Some people can have shortness of breath, cough, you know, and weight loss. Whereas other people may have no symptoms at all.
So again, the important thing here is that lung cancer can be diagnosed in anybody. All you really need to have is lungs. We see lung cancer in people who’ve smoked in the past, but we also see lung cancer in people who’ve never smoked. And that brings me to a really important point. Once we understand the histology, the type of cancer that it is, we then want to understand some of the biomarkers, right? What are biomarkers?
Biomarkers are distinct sort of entities that help us better understand things about your cancer. And allow us to potentially match people to therapies. So two biomarkers that we generally think about, one is molecular or mutational biomarkers. These are the mutations or abnormalities that led to the cancer. Two kinds of mutations. One is a germline mutation, which is inherited from mom and dad and has a risk of being passed on to your children.
These are uncommon in lung cancer. The second type is called a somatic mutation. And these are mutations that are acquired from the environment, from smoking, for example, from pollution, from radon. And these are not generally inherited mutations. So really important to understand mutational profile and ask your doctor, what is my mutation? Because we can then match people to targeted therapies. The second biomarker that is really important is something called PD-L1 or programmed death-ligand 1. I know it sounds exotic.
But that’s a biomarker that helps us guide how likely immunotherapy will work in your cancer. If the PD-L1 expression is high, greater than 50 percent, immunotherapy may be a very good option. If the PD-L1 expression is low, immunotherapy may sometimes be used, but more commonly in combination with chemotherapy. So my activation tip here is know what type of cancer you have, the histology. Whether it be adenocarcinoma or squamous cancer. And equally as important, know your biomarker, what mutation is driving your cancer and what PD-L1 expression your tumor harbors.
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Empowering Lung Cancer Patients | Embracing Hope, Treatment, and Teamwork
Empowering Lung Cancer Patients: Embracing Hope, Treatment, and Teamwork from Patient Empowerment Network on Vimeo.
What does the future of non-small cell lung cancer (NSCLC) treatment and care look like? Expert Dr. Samuel Cykert from UNC School of Medicine shares his outlook about the future of care and his advice to patients to help build emotional support.
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“…don’t give up, and one thing I’ve heard from patients over time, particularly among Black patients, there’s a tremendous faith community, and understanding that tremendous faith, faith is excellent, but also use that faith to understand that your belief in God, your interaction with God, God is using those doctors and those healthcare professionals to help you, so it’s not a solo effort, get everybody on the team.”
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Transcript:
Lisa Hatfield:
If you could give one suggestion to patients out there who may not be following up with their appointments, perhaps also in addition to the racial disparities? The unfortunate stigma surrounding lung cancer, and I wonder sometimes if that’s a barrier to continuing treatments or going to appointments, you could give one suggestion or sentence of encouragement to patients to seek out those high volume facilities if they’re diagnosed, if there’s a suspicion of lung cancer and to continue with treatment, what would your message be to those patients?
Dr. Samuel Cykert:
My message to patients, really it’s two-fold. On the medical side, lung cancer deaths are falling, all cancer deaths are falling, and they’re falling because of earlier detection, but they’re also falling because of these new treatments. And so it’s really, really important, particularly if you’re physically able, if you have a good functional status and you’re able to walk around and do things, it’s important that you really, really consider aggressive treatments because lung cancer isn’t an immediate death sentence anymore.
It is true that there are some lung cancers that are not curable, but with some of the new biologic treatments and chemotherapy regimens, people can live years with a good quality of life, even with some advanced lung cancers. So my advice on that side is don’t give up, and one thing I’ve heard from patients over time, particularly among Black patients, there’s a tremendous faith community, and understanding that tremendous faith, faith is excellent, but also use that faith to understand that your belief in God, your interaction with God, God is using those doctors and those healthcare professionals to help you, so it’s not a solo effort, get everybody on the team.
Lisa Hatfield:
Great message. Everybody on the team, I like that. Thank you, Dr. Cykert, and I appreciate all of your answers, and I’m hoping that this message, what people are watching that, understanding those statistics from your research, people who sometimes miss appointments or have transportation issues, maybe this will inspire them to continue finding ways to get there and to keep going, to keep fighting it and getting everybody on their team, I appreciate your message a lot. Thank you.
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What Urgent Innovations Can Advance Lung Cancer Precision Medicine?
What Urgent Innovations Can Advance Lung Cancer Precision Medicine? from Patient Empowerment Network on Vimeo.
How can non-small cell lung cancer (NSCLC) precision medicine be advanced through urgent innovations? Expert Dr. Samuel Cykert from UNC School of Medicine discusses technology and research innovations and epigenetics.
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Transcript:
Lisa Hatfield:
In your opinion, what are the most pressing research priorities or areas of innovation needed to further advance the implementation of biomarker testing and precision medicine in the management of lung cancer?
Dr. Samuel Cykert:
Yeah, there are two areas of this, the health services researcher side of me says institutions have to implement systems that follow patients in real time to making sure that they’re getting the testing and treatment that they need from the initial suspicion of lung cancer all the way to biomarker testing and therapies, whether they include surgery, chemo, radiation, biologics or immunotherapy. Those systems need to be areas of priority so that we’re really proactive of not only following patients, but from time to time, whether there are side effects or whether there is confusion, having those systems so we know when to re-engage patients when they’re not progressing along, so on the health services side, we have a lot of just phenomenal, phenomenal new treatments, and we have to make sure that every patient who is eligible is getting those treatments. Okay?
Now, on the other side of things, we’ve talked about racial disparities and other ethnic disparities in care, and one thing that people are observing over time is that in individuals and communities where racism is experienced, where the stress of racism is felt on a frequent basis, we know that outcomes are worse. And part of that may have to do with stress hormones themselves and how stress hormones interact with cancer treatments and hypertension treatment and other treatments, but the other possibility is there is a field called epigenetics, where genes change because of stressors.
And so it’s very conceivable now, in terms of the Human Genome Project, there is hardly a difference in the genome between white and Black people. Genetic race is a social construct, and genetically we’re almost identical, but if we’re experiencing epigenetics, if we are experiencing racism and that grind in daily life, it changes things within us, and so I think it’s important to get enough tissue on the research side from Black patients and other disadvantaged groups to look at the epigenetic part of it, because there may be new genes and new biomarkers we’re not experiencing now that are more prevalent in disadvantaged peoples, and so I think research has to go in that direction too, and even let’s talk about going upstream, maybe if we can prevent the effects of racism. I wish racism would end tomorrow, right, or today, but it doesn’t look like that’s happening. And so, is there any way we can attenuate the stresses of racism so that the downstream effects are prevented?
Lisa Hatfield:
Really interesting point you make about the stress of that. That’s super important. It’s something I hadn’t thought of. So thanks for mentioning that too.
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Tailored Approaches to Lung Cancer | The Crucial Role of Biomarker Testing
Tailored Approaches to Lung Cancer | The Crucial Role of Biomarker Testing from Patient Empowerment Network on Vimeo.
How does biomarker testing factor into personalized non-small cell lung cancer (NSCLC) treatment? Expert Dr. Samuel Cykert from UNC School of Medicine explains different ways that biomarker testing is used in personalizing treatment approaches and proactive patient advice for biomarker testing.
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“…have access to personalized medicine, whether it’s a surgical biopsy or a radiologic biopsy by a radiologist, you always make the statement. I would like biomarker testing for my biopsy specimen, and I would like to consider the testing that goes along with research protocols too.”
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Lisa Hatfield:
How does biomarker testing contribute to the personalized treatment approach for patients with non-small cell lung cancer, particularly in identifying actionable mutations like EGFR, BRAF, and other mutations?
Dr. Samuel Cykert:
Yeah, great, great question. Because some of these biomarkers tell you that there’s a specific treatment that will really, really work for you, and some of the biomarkers tell you there’ll be specific treatments that don’t.
And so the importance of them have to do with, again, you talk about personalized treatment, personalized treatment is getting a treatment that works for you, getting a treatment that works for the genetic component of your tumor, and so it’s really, really important that you differentiate, because again, there are studies that show certain immunotherapy medicines like pembrolizumab (Keytruda) and nivolumab (Opdivo), that those medicines will work in certain situations, but in other situations, they really don’t, and there are other medicines, for instance, tyrosine-kinase inhibitors that work, where in other situations, they don’t, and so it really is the definition of personalized medicine for lung cancer, knowing what’s going to work and what’s not going to work, and what your odds are in certain situations.
My activation tip is to have access to personalized medicine, whether it’s a surgical biopsy or a radiologic biopsy by a radiologist, you always make the statement. I would like biomarker testing for my biopsy specimen, and I would like to consider the testing that goes along with research protocols too.
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Catalyzing Lung Cancer Care | The Transformative Impact of Early Biomarker Testing
Catalyzing Lung Cancer Care: The Transformative Impact of Early Biomarker Testing from Patient Empowerment Network on Vimeo.
For non-small cell lung cancer (NSCLC) patients who receive early biomarker testing, what are the impacts? Expert Dr. Samuel Cykert from UNC School of Medicine discusses the benefits of biomarker testing and proactive advice for patients.
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“…make sure you discuss with the doctor who’s doing the biopsy that I really want biomarker testing at the beginning of treatment.”
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Lisa Hatfield:
Dr. Cykert, what are the main benefits of early and comprehensive biomarker testing in non-small cell lung cancer patients, and how does it impact treatment, decision-making, prognosis, and overall patient outcomes?
Dr. Samuel Cykert:
And 80 percent of patients with lung cancer are diagnosed with advanced disease, and really over the last half-dozen years, biomarker testing has become so important because in advanced disease, biological treatments have actually shown good benefits for a lot of patients and for some patients, just explosive benefits. And so on the treatment side, it’s very important to get a battery of biomarker tests, just to understand, as a patient, if you’re eligible for one of these treatments that are really good in terms of improving length and quality of life.
The second reason they’re important is a lot of work is being done on the research side of biomarker testing and biomarker treatments, so if a patient is to qualify for a really strong research study, biomarker testing is just something that’s very, very important. And so on the current treatment side and on the research side, there are really, really tremendous reasons to go ahead and get tested, and so my tip is since not every patient gets tested, make sure you discuss with the doctor who’s doing the biopsy that I really want biomarker testing at the beginning of treatment.
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