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Denise Brock

Lung Cancer Video Library – Spanish Language: Video #19 Second Line Therapy for NSCLC and ALK +

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GRACE Cancer Video Library - Lung

 

For our 19th video in the GRACE Spanish Lung Cancer Library, Dr. Brian Hunis, Medical Director, Head and Neck Cancer Program, Memorial Cancer Institute, Miami, Florida, joined GRACE to discuss the basics of Lung Cancer for Spanish-speaking patients and caregivers.  In this video Dr. Hunis discusses second line therapy for non-small lung cell cancer patients with anaplastic lymphoma kinase (ALK) positive.


 

 

 

 


 

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TRANSCRIPTS – Spanish and English
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Terapia de segunda línea para pacientes con cáncer pulmonar de células no pequeñas y con la cinasa de linfoma anaplásico (CLA) positiva.

Para los pacientes que progresaron a crizotinib, en este momento hay dos fármacos: ceritinib que se puede considerar si el paciente progresa con crizotinib, y hay otro fármaco llamado alectinib que es la tercera línea para pacientes que progresan en terapia dirigida para ALK.

Lo que uno tiene que saber, es que, por la resistencia adquirida a uno de estos fármacos, uno tiene que checar la biopsia porque puede ser que el paciente no responda a estas terapias y necesite quimioterapia.


Second line therapy for non-small lung cell cancer and with anaplastic lymphoma kinase (CLA) positive

For patients that progressed to crizotinib, in this moment there are two drugs available: ceritinib that can be considered if the patient progresses with crizotinib and the other drug is alectinib which is a third line treatment for patients that progressed with ALK targeted treatment.

What we have to know is that, for acquired resistance to one of these drugs, one has to check the biopsy because the patient might not respond to these therapies and might need chemotherapy.


ExecDirCarlea

Three Reasons to Be Hopeful About Lung Cancer

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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!

 


Dr West

Should Alecensa (Alectinib) be the new first line ALK inhibitor for ALK-positive NSCLC?

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Probably the most immediate potentially practice-changing presentation from ASCO was the Japanese J-ALEX study in the subset of about 4-5% of patients with non-small cell lung cancer (NSCLC) who have the molecular driver known as an anaplastic lymphoma kinase (ALK) rearrangement, which we now routinely test for from the tumor tissue of patients with a non-squamous metastatic NSCLC.   The current historical standard of care as first line treatment is Xalkori (crizotinib), which is an ALK inhibitor that happened to be readily available when the ALK rearrangement was first being studied in NSCLC about 5-7 years ago. Though it was granted an accelerated FDA approval back in 2011 based on early very promising activity and has since been confirmed to be superior to chemotherapy as first line treatment in ALK-positive patients, it is a less active ALK inhibitor than many other “second-generation” ALK inhibitors such as Zykadia (ceritinib) and Alecensa (alectinib), both now FDA-approved for patients who have developed progression after Xalkori or who are not able to tolerate it, as well as other agents still in development, including brigatinib (likely to become approved soon), and a few others further behind in development but also very active against ALK-positive NSCLC.

A question that logically follows is whether it is better to give one of these more active second generation ALK inhibitors as first line therapy, where they are likely to be more active for longer than if given for “acquired resistance” after Xalkori, or whether it’s better to start with Xalkori and have other powerful ALK inhibitors left for later.  Should we use our best drug up front or only the most effective drug required to do the job for now, saving something in the tank as we think more about advanced lung cancer as a distance race than a sprint? How much do we prioritize control now vs. options later?

There are several trials that have been initiated that all test a second generation ALK inhibitor vs. Xalkori.  Two of the first to be completed compare Alecensa to Xalkori, a large, global trial known as ALEX, and a smaller trial done in Japan only, known as J-ALEX, which reported early and remarkably interesting results at ASCO 2016.

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GRACE Video

Platinum-Based Chemo Doublets: Backbone for NSCLC Treatment

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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.

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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.


GRACE Video

Timing of Second Generation ALK Inhibitors: First Line vs. Treatment after Acquired Resistance

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Dr. Ross Camidge, University of Colorado, addresses the question of whether to use a second generation ALK inhibitor as first line therapy or only after acquired resistance to crizotinib.

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Transcript

One of the long-standing philosophies in oncology is you use your best drugs first. To be honest that goes back to a mindset that maybe people weren’t going to survive for you to try a treatment in a second line or third line setting, so you were just trying to get in your best drug in whilst you had a chance. Now we’ve seen with the next generation ALK inhibitors, they have better activity in the brain, they have activity after crizotinib has stopped working, so the logical question is, what if you come in with these drugs first instead of crizotinib? Could they displace the recently crowned king of ALK crizotinib by being the new pretender? Well, maybe.

The only direct head to head study is with alectinib and that’s the so-called ALEX study — alectinib, ALE, compared to crizotinib which is also called Xalkori and that’s where the X comes from — ALEX. There’s a very similar study run in Japan which is called the J-ALEX study. Both of those have finished accrual, so we should see those results in the near future.

Now, when we get that data it’s going to be very interesting to look at. Does the alectinib just have to be better that the crizotinib? Well, sure, it probably has to be and it probably will be. The real question is, how much better? If it’s just a little bit better, sure that’s a positive study, they’ll get a license for the drug, but you could still use crizotinib followed by alectinib, or followed by any other second generation ALK inhibitor, and maybe that sequential benefit may be more than if you use your best card up first.

What if it’s the same as the sequential therapy? Well that might change peoples’ prescribing if the drug is better tolerated, more convenient, or cheaper, and new drugs tend not to be cheaper. Perhaps what we’re hoping for is that by suppressing some of the dominant mechanisms of resistance from the get go, we’ll actually change the natural history of the disease. Every time resistance occurs, more cells divide, they grow up, and they’re generating the next and the next mechanism of resistance.

So the more you can suppress cell turnover from the get go, the more maybe you can extend out the overall duration of control — but we have to wait for those results to come out and until they come out, I wouldn’t start using second generation inhibitors in the first line setting without that data.


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