GRACE :: Lung Cancer

EGFR

Denise Brock

Lung Cancer Video Library – Spanish Language: Video #31 EGFR Mutation: What Is It, and Which Patients Have It?

Share
 
GRACE Cancer Video Library - Lung

 

We continue to provide informational videos for our Spanish speaking community and welcome Dr. Luis Raez, MD FACP FCCP, Chief of Hematology/Oncology and Medical Director at Memorial Cancer Institute, and Clinical Associate Professor of Medicine at Florida International University.  Dr. Raez joined GRACE to discuss the basics of lung cancer.  In this 31st video for the Spanish lung cancer video library, Dr. Raez discusses EGFR mutation: what is it, and which patients have it?


 

How Did You Like This Video?

Please feel free to offer comments and raise questions in our Discussion Forums.


 

TRANSCRIPTS – Spanish and English
download transcripts
 

Mutación del receptor del factor de crecimiento epidérmico (EGFR): ¿Qué es? Y ¿Qué pacientes lo tienen?

Mutation of the epidermal growth factor receptor (EGFR): What is it? And, what patients have it?

 

 Dr. Luis Raez, MD FACP FCCP

Chief of Hematology/Oncology and Medical Director, Memorial Cancer Institute,
Clinical Associate Professor of Medicine, Florida International University

 

Spanish TRANSCRIPT

Este es un tópico nuevo, pero ya después de cuatro-cinco años de hablar de él, mucha gente ya está familiarizada.

Básicamente las mutaciones EGFR son mutaciones en el receptor EGFR que se localizan específicamente en áreas del cromosoma que son los exones 19 y 21. En esas dos áreas del cromosoma que son esos dos exones, las mutaciones que representa el receptor hace que se sensibilice el receptor para que responda a las terapia blanco. Hemos tenido mucha suerte que ya se hayan aprobado fármacos como gefitinib, erlotinib, afatinib que son fármacos que atacan a los tumores que expresan estas mutaciones.

Esta sensibilidad lamentablemente no es permanente, con el tiempo de repente, en unos 10 o 12 meses, se empieza a ver resistencia. Muchas veces estos pacientes están con estas terapias blanco por 10 o 12 meses y después tenemos que cambiar de terapia cuando hay nuevas nutaciones en otros exones que crean resistencia.

Es importante saber que hay que buscar estas mutaciones en los pacientes con cáncer de pulmón. Son mutaciones tumorales, no son mutaciones de línea germinal como en cancer de mama. En el cáncer de mama, se buscan oncogenes como el gen BRCA. Pero todo lo que hablamos del cancer de pulmón, todas las mutaciones se buscan en el tumor.

Hoy en día hemos tenido la suerte de poder identificar DNA tumoral en la sangre. Entonces muchas veces estas mutaciones EGFR se pueden buscar en la sangre o en la orina de los pacientes. Así que podríamos de repente evitar tener que repetir o hacer biopsias, si es que podemos detectarlo en la sangre o en la orina para ayudar a diagnosticar esta mutación.


 

English TRANSCRIPT

This is a new topic, but after four or five years of talking about it, people are getting to know it better.

Basically, mutations in the EGFR are in its receptor and they are located in areas of the chromosome that are the exons 19 and 21. In those two exons, mutations that are represented in the receptor, sensitize it to be able to respond to targeted therapies. We’ve been very lucky in the approval of drugs like gefitinib, erlotinib and afatinib, that are drugs that target tumor with these mutations.

Unfortunately, this sensitivity is not permanent. With time, around 10 to 12 months, resistance starts. Many times these patients are in targeted therapies for 10-12 months, and then we have to change therapy because of new mutations in other exons that are creating resistance.

It’s important to know that we have to search for new mutations in lung cancer patients. They are tumoral mutations and not germline mutations like in breast cancer. In breast cancer, we look for oncogenes mutations like in BRCA. But in lung cancer, all the mutations we look for are in the tumor.

Nowadays, we’ve been very lucky to be able to identify tumoral DNA in blood. So, many times, these EGFR mutations can be identified in the blood or urine of the patients. With this, we would be able to avoid biopsies or have to repeat them.


Denise Brock

Targeted Therapies in Lung Cancer Patient Forum 2016 – Breakout Session EGFR

Share

Presented by the

Global Resource for Advancing Cancer Education
in collaboration with
the University of Colorado
Cancer Center
 
On August 20, 2016, in collaboration with the University of Colorado Cancer Center, GRACE presented the Targeted Therapies in Lung Cancer Patient Forum in Aurora Colorado. We are happy to share the videos from this live and webcast forum. Our sixth video is from the forum breakout session for EGFR patients and caregivers, featuring co-chairs Dr. Greg Riely and Dr. Jack West, and patient moderator Bob Fuerst.

Download the Agenda and Speaker Bios

(click for speaker slides)
EGFR – Acquired Resistance Treatment Options
EGFR – The Road to Resistance
 


How Did You Like This Video?

Please feel free to offer comments and raise questions in our Discussion Forums.

 

ExecDirCarlea

Three Reasons to Be Hopeful About Lung Cancer

Share

2016 Targeted Therapies Forum

The medical community has made significant progress in understanding that lung cancer is not a single cancer, and are treating it accordingly. We’ve stopped carpet bombing the body and have started using targeted weaponry to assassinate some forms of cancer. As a result, some patients are alive now, over a decade after being diagnosed with metastatic lung disease.

We can credit much of that progress to research into three specific mutations that drive distinctive forms of lung cancer. Instead of treating patients with these different mutations the same, we now give them individualized treatments that work differently based on their cancer’s mutation.

If you or someone you know is diagnosed with non-small cell lung cancer (NSCLC), there are three major subtypes the cancer should be tested for:

  1. ALK positive. A change in the cancer’s ALK gene allows the cancer cell to grow uncontrollably, but several drugs on the market have shown incredible responses and durations of disease control for patients. Even patients’ whose cancer has spread to the brain are now living years, not just weeks.
  2. ROS1 positive. A change in the cancer’s ROS1 gene, which is similar to the ALK gene, makes cancer cells grow and divide. Only one to two percent of lung cancer patients have it but with one highly effective drug on the market and several others being explored in clinical trials, even rare subtypes of cancers are focusing the attention of scientists, physicians, and the pharmaceutical industry alike.
  3. EGFR mutant. This was the first molecular marker that really showed a test done on lung cancer could predict who would respond to a specific targeted treatment. Now, our increased understanding of how the cancer can later evolve to grow in the presence of the first generation drugs has led to the development of next generation therapies which can regain cancer control in nearly 60% of cases, giving patients a second lease on life.

It is hard to overstate the awesomeness of these breakthroughs.

Around the world, a diagnosis of lung cancer leads to more cancer-related deaths than those from breast cancer, colorectal cancer, prostate cancer, and pancreas cancer combined. Yet for a growing number of distinct molecular subtypes of this disease, even advanced lung cancer can now be a controllable disease. Beyond the three subtypes described above, many other different mutations and genetic changes which could allow lung cancer therapy to be personalized are receiving testing in clinical trials. Most recently, the advent of immunotherapy – using drugs to stimulate the body’s own immune system to attack the lung cancer – has also shown promise, and how these two areas – personalized medicine and immunotherapy – will overlap and interact represent some of the major research directions for the future.

So, this is great news, right? Oncologists throughout the country are testing their patients’ tumors, and people are living longing and better than they could have ever imagined, yes?

No.

Despite all of this great news, many NSCLC patients do not get their tumors tested for ALK, ROS1, or EGFR mutations. Improving these numbers falls to the patients or their caregivers to educate themselves and advocate for molecular testing.

Fortunately, organizations like the Global Resource for Advancing Cancer Education (GRACE) exist solely to help patients become shared decision makers when it comes to their cancer care

GRACE is working with the University of Colorado Cancer Center in Aurora to hold a patient event on Aug. 20th for those living with ALK, ROS1, or EGFR mutant lung cancers. The organizers have already solicited questions in advance from patients in the internet lung cancer community.

The Targeted Therapies in Lung Cancer Patient Forum is open to patients and their caregivers. Renowned lung cancer experts from around the U.S. will present, and patients who are living with lung cancer will serve as moderators of the discussions that take place between the doctors and the audience.

The morning sessions will help attendees understand their mutation, learn of open clinical trials, and hear about treatment options;.all to help patients develop their plans A, B, C, and D. The afternoon will focus on survivorship in all its aspects, from finances to sex, to diet, to exercise – how to live life to the fullest with lung cancer.

Register today!

 


GRACE Video

Rociletinib/Osimertinib for EGFR T790M-negative NSCLC

Share
GRACE Cancer Video Library - Lung

GCVL_LU-F13_Rociletinib_Osimertinib_EGFR_T790M-Negative_NSCLC

 

Dr. Jack West, Swedish Cancer Institute, reviews trial evidence for the efficacy of rociletinib and osimertinib for EGFR acquired resistance not driven by a T790M mutation.

Download Transcript

How Did You Like This Video?

Please feel free to offer comments and raise questions in our Discussion Forums.

 

Transcript

For patients who have an activating mutation in their cancer known as EGFR we have several very good first line treatment options to consider. There are three leading contenders as oral targeted therapies that block EGFR and tend to work very well for patients with an EGFR mutation. These agents are known as Iressa (gefitinib), Tarceva (erlotinib), and Gilotrif (afatinib). These agents have a chance of shrinking the tumor in the range of 60% to 75% which is great, but unfortunately these responses do not last forever and on average, patients will develop progression of their cancer, so-called acquired resistance to this first line therapy, after something in the range of nine to 12 months — can be less, can be more.

The question is what to do when that occurs. Well, there are a couple of agents that have shown great promise and great activity, at least in the subset of patients who have a mutation, found at the time of this acquired resistance, that is known as T790M. And so we repeat a biopsy of an area of progressing cancer while patients are on and progressing on this first line EGFR inhibitor, and 50% or 60% will have this acquired resistance mutation known as T790M. For those patients, we standardly consider drugs like osimertinib and rociletinib, and I say standardly consider as if they’re commercially available, and they’re not yet, at this moment in late 2015, FDA approved but it is expected that both will be approved by the FDA based on their very good activity in the very near future, perhaps by the time you see this.

But these agents are best studied and have their greatest activity in the patients with a T790M mutation. So what about the patients who are still 40% or 50% of that population with progressing cancer on an EGFR inhibitor who don’t have a T790M mutation? It turns out that both of these agents have good activity, or at least some degree of activity, in patients who are T790M-negative. It doesn’t tend to be as long-lasting and the response rates tend to be lower, but the activity is certainly encouraging.

GCVL_LU-XXNN_Jack_West_Swedish_15_01

When you look at what’s called a waterfall plot that’s shown here of how patients respond, the bars going downward represent patients whose cancers have shrunk, and the ones that go upward are the ones whose cancers have progressed on a therapy. You can see that when we look at patients who received osimertinib, the AstraZeneca drug AZD9291, there is good activity in the majority of patients who receive this agent, even if they have no T790M mutation.

GCVL_LU-XXNN_Jack_West_Swedish_15_02

The same is true for rociletinib, the Clovis drug CO1686 — the waterfall plot shows that most of the bars do go down, and that a lot of patients receive a substantial benefit, even if they do not have T790M detected in their rebiopsied tumor.

So there are studies that are looking specifically at these agents in patients who are T790M-negative. A trial with rociletinib known as TIGER-3 is looking at patients who have received prior EGFR inhibitors like Iressa, Tarceva or Gilotrif, and have also received prior chemotherapy. These patients are then randomized to either receive rociletinib or a standard chemotherapy as a single agent, and there are several that your doctor can choose from. This trial will be looking at which patients do better depending on whether they get the targeted therapy or standard chemotherapy.

There is another trial being done with osimertinib in combination with an EGFR monoclonal antibody known as necitumumab, so a two drug combination being looked at in patients who are T790M-negative after progressing on a first line EGFR inhibitor. So both of these agents are being studied not just in patients with a T790M-positive cancer, but a T790M-negative cancer, and if you do have acquired resistance and are found to not have a T790M mutation, you might want to look into information about these trials to see if one might be a good choice for you.


GRACE Video

Platinum-Based Chemo Doublets: Backbone for NSCLC Treatment

Share

GRACEcast-515_Lung_West_Platinum_Based_Chemo_Doublets_Backbone_NSCLC_Treatment

 

Dr. Jack West, Swedish Cancer Institute, identifies the platinum-based chemotherapy doublet as the backbone of first-line treatment for the majority of NSCLC patients.

Download Transcript

How Did You Like This Video?

Please feel free to offer comments and raise questions in our Discussion Forums.

 

Transcript

The most common subtype of lung cancer is known as non-small cell lung cancer which comprises about 87% or 88% of all of the lung cancers out there. One of the big challenges in managing lung cancer and non-small cell lung cancer specifically is that about half of patients are diagnosed at a time when they already have stage IV or metastatic disease. At that time, this is not a cancer that we can treat to cure it, but our goal is to prolong survival as much as possible and also to minimize the cancer-related symptoms, as well as the treatment-related side effects.

Over the last 10 to 15 years we’ve really clarified the best approach in terms of chemotherapy for the majority of people with advanced non-small cell lung cancer. Now, chemotherapy is the optimal approach for patients who do not have a so-called driver mutation, which is an uncommon mutation such as EGFR or ALK or ROS1 that you may hear about which are present in a minority of patients with advanced non-small cell lung cancer, but the majority of patients don’t have one of these driver mutations.

For that majority who don’t have a driver mutation, the optimal treatment approach is standard two-drug chemotherapy. This is specifically called a platinum-based doublet and it’s called that because the main component or the first component is a drug called cisplatin or carboplatin that has been studied for many years and is paired with another drug such as Taxol, also known as paclitaxel, or Taxotere, known as docetaxel as well, Gemzar, also known as gemcitabine, Alimta, also known as pemetrexed, or occasionally other agents.

These two-drug combinations have been compared in many trials and really shown to be essentially remarkably similar if not identical in efficacy. Because of that, we usually choose the treatment, the two-drug combination, to recommend based on issues such as convenience to the patient — some of them are every week administration, others are every three weeks; for some patients coming in a long distance, three-week treatment is much more convenient. Some have hair loss, some do not, and also some of these agents may be particularly a little more effective in some subtypes of non-small cell lung cancer — known as the particular histology, and others might be a better choice for a different histology.

We’re going to talk about that specific difference and which regimens we might exactly recommend for one subtype or another in other videos, but right now it’s important just to note that the mainstay of treatment for the patients who don’t have a driver mutation, in the first line setting, is a two-drug platinum-based combination — cisplatin or carboplatin, with a partner drug, and they really do seem to produce very comparable results.

We’ll talk about some potential specific differences in other videos.

Thanks.


Ask Us, Q&A
Lung/Thoracic Cancer Expert Content

Archives

Share

GRACE Cancer Video Library - Lung Cancer Videos

 

2015_Immunotherapy_Forum_Videos

 

2015 Acquired Resistance in Lung Cancer Patient Forum Videos

Share

Join the GRACE Faculty

Breast Cancer Blog
Pancreatic Cancer Blog
Kidney Cancer Blog
Bladder Cancer Blog
Head/Neck Cancer Blog
Share

Subscribe to the GRACEcast Podcast on iTunes

Share

Email Newsletter icon, E-mail Newsletter icon, Email List icon, E-mail List icon

Subscribe to
GRACE Notes
   (Free Newsletter)

Other Resources

Share

ClinicalTrials.gov


Biomedical Learning Institute

peerview_institute_logo_243