FDA Approves Zykadia (Ceritinib) for ALK-Positive Lung Cancer

gdpawel

A second drug that specifically targets non-small cell lung cancer (NSCLC) that is positive for the ALK gene rearrangement has been approved by the US Food and Drug Administration (FDA).

The new drug, ceritinib (Zykadia, Novartis), in indicated for patients with ALK-positive NSCLC who have previously been treated with crizotinib (Xalkori, Pfizer), the first targeted agent for this patient population.

This is an accelerated approval, and comes 4 months ahead of schedule.

ALK gene rearrangement is found in about 2% to 7% of patients with NSCLC, which makes up about 85% of all lung cancer, according to the FDA announcement.

Since its launch in 2011, crizotinib has become a standard of care in this small patient population, with data showing that it doubles progression-free survival when compared with chemotherapy.

However, some patients become resistant to crizotinib, and until now, there has been no other targeted therapy to offer these patients. Zykadia (ceritinib now fills that role.

"Ceritinib represents an important treatment option for ALK-positive NSCLC patients who relapse after starting initial therapy with crizotinib," said lead investigator Alice Shaw, MD, PhD, from the Massachusetts General Hospital Cancer Center in Boston. "This approval will affect the way we manage and monitor patients with this type of lung cancer, as we will now be able to offer them the opportunity for continued treatment response with a new ALK inhibitor," she said in a statement.

The drug went through the FDA Accelerated Approval Program, which allows approval of a drug to treat a serious or life-threatening disease based on clinical data showing the drug has an effect on a surrogate end point reasonably likely to predict clinical benefit to patients. This program provides earlier patient access to promising new drugs while the company conducts confirmatory clinical trials, the agency said.

The accelerated approval was based on a clinical trial of 163 patients with metastatic ALK-positive NSCLC, who progressed on or were intolerant to treatment with crizotinib. The most common sites of metastases in the patient population studied were brain (60%), liver (42%), and bone (42%)

Results showed that about half of the participants had their tumors shrink, and this effect lasted an average of about 7.0 months, the agency noted. The overall response rate was 54.6% (95% confidence interval [CI], 47% - 62%), and the median duration of response was of 7.4 months (95% CI, 5.4 - 10.1), the company added in its press release.

Common adverse effects of Zykadia (ceritinib) include gastrointestinal symptoms, such as diarrhea, nausea, vomiting, and abdominal pain. Laboratory abnormalities, such as increased liver enzymes, pancreatic enzymes, and increased glucose levels, were also observed.

It was approved 4 months ahead of the product's prescription drug user fee goal date of August 24, the date the agency was scheduled to complete review of the drug application.

The FDA also granted Zykadia (ceritinib) Breakthrough Therapy Designation, priority review, and Orphan Product Designation. The manufacturer has demonstrated through preliminary clinical evidence that the drug may offer a substantial improvement over available therapies, the agency said. It had the potential, at the time the application was submitted, to be a significant improvement in safety or effectiveness in the treatment of a serious condition. Also, the drug is intended to treat a rare disease, it noted.

Citation: FDA Approves Ceritinib for ALK-Positive Lung Cancer. Medscape. Apr 29, 2014.

Approval After Phase I: Ceritinib Runs the Three-Minute Mile

http://theoncologist.alphamedpress.org/site/misc/TO_CeritinibRunsthe3MinuteMile.pdf

gdpawel

The problem with ALK-rearranged NSCLC targeted drug Zykadia

Zykadia (ceritinib) being approved is a good thing as it is yet another drug that may provide good benefit for some or even possibly many people. The real question is whether it is right for a specific patient with a specific cancer. The answer to that is they don't know because they don't even bother to test for it. They simply test whether the mutation or gene structure exists in the cancer patient for which this drug might be of use. Without any other compelling testing or data on actual use and effect of the drug on that specific cancer patient the odds will always be 50/50, as it is pointed out in how we perform trial and error medicine.

The problem here isn't whether Zykadia is an effective drug or not, it's the same problem they still refuse to deal with and that is whether it is an effective drug or not for each specific patient, the whole purpose of targeted therapy. The assumption is that because you have the mutation (the specific focus) which a drug is related too, it should have some effect and does not account for anything else of which there are and has already been pointed out, seemingly limitless factors. It costs entirely too much to study and determine all of these things, they just want what they need to get approved.

It is so much more complex than that and is why Zykadia has great effect in one and little to none in another even though the tests they currently use say it should work simply because they assume it will as they have the same mutation. Truth is, without proper whole cell live assay testing done on a proper sample, the only way to know if it will work or not is trial and error, the very way they do treatment today, take the drug over a period of time and see if it is working or not. Mutation testing to find targeted drugs is good but it is only a piece to the puzzle and does not really indicate whether it will work for one patient over another with the same mutation. If it did, every single patient with the mutation would benefit exactly the same with the same drug, it simply just doesn't work like that even though that is the basis of the primary treatment assumption for all cancers and all treatments.

So, besides not approaching drug selection and treatment properly to begin with the other big factor is of course cost which many governments and insurance providers are becoming more and more unwilling to justify.

Nobody is looking for a cure, it gets thrown around a lot because that's what they all wish for. Truth is every cancer and every patient is unique so there is likely no cure-all, at least not with the knowledge they have today. We have treatments and a good focus for treatment is to turn cancer into a cronic condition which can be maintained and controlled until natural death occurs. Very slowly the focus in the US is switching to that but it will probably take some time. Disease stability is something that can be achieved if they focus on it properly and both PFS, OS and QOL are all part of the equation. PFS and OS can be definitive, QOS is subjective so very difficult to quantify properly.

The Downside To Clinical Trials

http://cancerfocus.org/forum/showthread.php?t=4040

gdpawel

gdpawel said:

The problem with ALK-rearranged NSCLC targeted drug Zykadia

Zykadia (ceritinib) being approved is a good thing as it is yet another drug that may provide good benefit for some or even possibly many people. The real question is whether it is right for a specific patient with a specific cancer. The answer to that is they don't know because they don't even bother to test for it. They simply test whether the mutation or gene structure exists in the cancer patient for which this drug might be of use. Without any other compelling testing or data on actual use and effect of the drug on that specific cancer patient the odds will always be 50/50, as it is pointed out in how we perform trial and error medicine.

The problem here isn't whether Zykadia is an effective drug or not, it's the same problem they still refuse to deal with and that is whether it is an effective drug or not for each specific patient, the whole purpose of targeted therapy. The assumption is that because you have the mutation (the specific focus) which a drug is related too, it should have some effect and does not account for anything else of which there are and has already been pointed out, seemingly limitless factors. It costs entirely too much to study and determine all of these things, they just want what they need to get approved.

It is so much more complex than that and is why Zykadia has great effect in one and little to none in another even though the tests they currently use say it should work simply because they assume it will as they have the same mutation. Truth is, without proper whole cell live assay testing done on a proper sample, the only way to know if it will work or not is trial and error, the very way they do treatment today, take the drug over a period of time and see if it is working or not. Mutation testing to find targeted drugs is good but it is only a piece to the puzzle and does not really indicate whether it will work for one patient over another with the same mutation. If it did, every single patient with the mutation would benefit exactly the same with the same drug, it simply just doesn't work like that even though that is the basis of the primary treatment assumption for all cancers and all treatments.

So, besides not approaching drug selection and treatment properly to begin with the other big factor is of course cost which many governments and insurance providers are becoming more and more unwilling to justify.

Nobody is looking for a cure, it gets thrown around a lot because that's what they all wish for. Truth is every cancer and every patient is unique so there is likely no cure-all, at least not with the knowledge they have today. We have treatments and a good focus for treatment is to turn cancer into a cronic condition which can be maintained and controlled until natural death occurs. Very slowly the focus in the US is switching to that but it will probably take some time. Disease stability is something that can be achieved if they focus on it properly and both PFS, OS and QOL are all part of the equation. PFS and OS can be definitive, QOS is subjective so very difficult to quantify properly.

The Downside To Clinical Trials

http://cancerfocus.org/forum/showthread.php?t=4040

Those on Xalkori but their NSCLC worsened or cannot tolerate it

Zykadia (ceritinib) is a new FDA-approved prescription medicine that is used to treat people with non-small cell lung cancer (NSCLC) that:

* Is caused by a defect in a gene called anaplastic lymphoma kinase (ALK), and
* Has spread to other parts of the body, and
* Who have taken the medicine crizotinib, but their NSCLC worsened or they cannot tolerate taking crizotinib

The effectiveness of Zykadia (ceritinib) is based on response rate and duration of response. There are no data demonstrating an improvement in patient reported outcomes or survival with Zykadia (ceritinib).

If you or a loved one has been diagnosed with ALK+ NSCLC and have already received an ALK inhibitor, ask your doctor if Zykadia (ceritinib) may be right for you. Make an appointment to talk to your doctor today.

IMPORTANT INFORMATION AND INDICATION FOR ZYKADIA (ceritinib) CAPSULES

What is the most important information I should know about ZYKADIA?

Zykadia (ceritinib) may cause serious side effects, including:

*Stomach and intestinal problems.

Zykadia (ceritinib) causes stomach and intestinal problems in most people, including diarrhea, nausea, vomiting, and stomach-area pain. These problems can sometimes be severe. Follow your health care provider's instructions about taking medicines to help these symptoms. Call your health care provider for advice if your symptoms are severe or do not go away.

* Liver problems.

Zykadia (ceritinib) may cause liver injury. Your health care provider should do blood tests at least every month to check your liver while you are taking Zykadia. Tell your health care provider right away if you get any of the following:

you feel tired
have itchy skin
your skin or the whites of your eyes turn yellow
you have nausea or vomiting
you have a decreased appetite
you have pain on the right side of your stomach-area
your urine turns dark or brown (tea color)
you bleed or bruise more easily than normal

* Lung problems (pneumonitis).

Zykadia may cause severe or life-threatening swelling (inflammation) of the lungs during treatment that can lead to death. Symptoms may be similar to those symptoms from lung cancer. Tell your health care provider right away if you have any new or worsening symptoms, including:

trouble breathing or shortness of breath
cough with or without mucous
fever
chest pain

* Heart problems.

Zykadia may cause very slow, very fast, or abnormal heartbeats. Your health care provider may check your heart during treatment with Zykadia. Tell your health care provider right away if you feel new chest pain or discomfort, dizziness or lightheadedness, faint, or have abnormal heartbeats. Tell your health care provider if you start to take or have any changes in heart or blood pressure medicines.

See "What are possible side effects of Zykadia?" for more information about side effects.

What is Zykadia?

Zykadia is a prescription medicine that is used to treat people with non-small cell lung cancer (NSCLC) that:

is caused by a defect in a gene called anaplastic lymphoma kinase (ALK), and
has spread to other parts of the body, and
who have taken the medicine Xalkori (crizotinib), but their NSCLC worsened or they cannot tolerate taking Xalkori (crizotinib)

It is not known if Zykadia is safe and effective in children.

What should I tell my health care provider before taking Zykadia?

Before you take Zykadia, tell your health care provider about all of your medical conditions, including if you:

have liver problems
have diabetes or high blood sugar
have heart problems, including a condition called long QT syndrome
are pregnant or plan to become pregnant. Zykadia may harm your unborn baby. Women that are able to become pregnant should use an effective method of birth control during treatment with Zykadia and for up to 2 weeks after stopping Zykadia. Talk to your health care provider about birth control methods that may be right for you
are breastfeeding or plan to breastfeed. It is not known if Zykadia passes into your breast milk. You should not breastfeed if you take Zykadia

Tell your health care provider about the medicines you take, including prescription medicines, over-the-counter medicines, vitamins, and herbal supplements.

How should I take Zykadia?

Take Zykadia exactly as your health care provider tells you. Do not change your dose or stop taking unless your health care provider tells you to
Take Zykadia 1 time each day
Take Zykadia on an empty stomach, do not eat for 2 hours before and do not eat for 2 hours after taking Zykadia
If you miss a dose of Zykadia, take it as soon as you remember. If your next dose is due within 12 hours, then skip the missed dose. Just take the next dose at your regular time

What should I avoid while taking Zykadia?

You should not drink grapefruit juice or eat grapefruit during treatment with Zykadia. It may make the amount of Zykadia in your blood increase to a harmful level

What are the possible side effects of Zykadia?

Zykadia may cause serious side effects, including:

See "What is the most important information I should know about Zykadia?"

High blood sugar (hyperglycemia). People who have diabetes or glucose intolerance, or who take a corticosteroid medicine have an increased risk of high blood sugar with Zykadia. Follow your health care provider's instructions about monitoring your blood sugar. Call your health care provider right away if you have any symptoms of high blood sugar, including:

increased thirst
increased hunger
headaches
trouble thinking or concentrating
urinating often
blurred vision
tiredness
your breath smells like fruit

The most common side effects of Zykadia include:

stomach and intestinal problems. See "What is the most important information I should know about Zykadia?"

tiredness, decreased appetite, and constipation

These are not all of the possible side effects of Zykadia. For more information, ask your health care provider or pharmacist. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

General information about the safe and effective use of Zykadia

Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use Zykadia for a condition for which it was not prescribed. Do not give it to other people, even if they have the same symptoms you have. It may harm them. You can ask your health care provider or pharmacist for more information about Zykadia.

Click here for full Prescribing Information.

http://www.pharma.us.novartis.com/product/pi/pdf/zykadia.pdf?site=EK000007&source=01025&irmasrc=NA 

Sincerely,

The Zykadia Team

Novartis Pharmaceuticals Corporation

Now that it's FDA approved, phenotype assayists are ordering some and building up a database, to give it to the right patients. There is entirely too much trial-and-error giving so much side effects to the wrong patients.