More on Crizotinib

Pfizer Inc.'s just-approved drug Xalkori, the first new medicine in more than six years for deadly lung cancer, proves the value of precisely targeting rare diseases linked to gene variants, cancer specialists and Pfizer executives said Tuesday.
The drug was approved Friday in the U.S. along with a companion diagnostic test for just a small subset of lung cancer patients. It epitomizes drugmakers' new strategy of developing very expensive but effective medicines for relatively few patients to replace the blockbusters for the masses now getting competition from generic drugs.
It's also in the vanguard of long-awaited personalized medicine, in which doctors identify patients with gene changes or variations that fuel their disease and then try to match them with new medicines that specifically target those genes.
"This is a paradigm shift," Dr. Paul A. Bunn Jr., a University of Colorado professor and cancer researcher involved in testing Xalkori, told journalists during a conference call hosted by Pfizer. "It used to be that everybody with cancer was treated the same," with surgery and chemotherapy.
Xalkori, a pill with relatively minor side effects compared to the hair loss and nausea that chemotherapy can cause, was approved for the roughly 4 percent of patients with advanced nonsmall cell lung cancer who have what's called the ALK fusion gene.
When ALK, short for anaplastic lymphoma kinase, and another gene on the same chromosome rearrange their positions and fuse together, the ALK gene stays on constantly, fueling cancer cell growth. Xalkori works by blocking the kinase enzyme, key to that process.
About 6,000 Americans a year develop this cancer, Pfizer said. Those patients, called ALK positive, now can be identified with a $250 molecular diagnostic test developed by Pfizer's partner, Abbott Molecular Oncology. The test was also approved Friday.
"You're going to be sparing individuals side effects (and) the waste of resources, time and drug that really isn't going to help them," Dr. Mark Kris, head of the thoracic oncology service at Memorial Sloan-Kettering Cancer Center in New York, said during the call.
Normally doctors choose among different chemotherpay regimens for each patient, and they may not pick an effective one.
In Pfizer-funded early and midstage studies that led to Xalkori's approval, tumors disappeared, shrank or stopped growing in just over half of patients for nearly two years on average. Research to determine overall survival is ongoing.
By comparison, nonsmall cell lung cancer – about 85 percent of cancer cases – is tough to treat and kills nearly 95 percent of patients within five years. Lung cancer is the top killer among cancers worldwide.
Xalkori, known chemically as crizotinib, costs about $9,600 a month and is taken until it stops fighting tumors, at which point patients likely would be put on older chemo drugs they hadn't taken yet. Pfizer has started a Xalkori patient assistance program with a maximum $100 monthly copayment for insured patients meeting certain financial limits. Insurers are expected to cover the drug for ALK-positive patients.
Jeff Wigbels, an investment bank portflio manager treated in one of the drug studies, said when he started taking it, he couldn't eat because cancer had spread to his throat. Within a week he could eat again and soon scans of his lung and throat no longer showed tumors.
"It was just an amazing experience," he said.
Another patient, Richard Heimler, a former nonprofit executive, said he had one cancerous lung removed seven years ago and repeatedly had new tumors surgically removed from his brain and the other lung, along with chemotherapy. He began taking Xalkori 15 months ago and still takes a pill twice a day.
"My tumors have either disappeared, shrunk or are stable," said Heimler, and he's functioning well again.
Pfizer is currently running two late-stage studies that compare Xalkori to different chemotherapy treatments that have been the standard of care. It's unusual to get approval before completing such large, late-stage studies. Xalkori was approved remarkably quickly, just four years after Japanese researchers reported they had identified the ALK gene variation.
Pfizer is awaiting approval from regulators in the European Union, Switzerland, Japan and Korea, and also is testing crizotinib against other types of cancer.
Pfizer said 3 percent to 5 percent of patients with nonsmall cell lung cancer have the ALK gene fusion. But one research group presented data at a recent cancer conference showing 8 percent of those patients have it.
Pfizer needs some big sellers because its $10.7 billion-a-year cholesterol fighter, Lipitor, the world's top-selling drug, loses U.S. patent protection on Nov. 30. That starts an unprecedented wave of much-cheaper generic versions of many drugs taken daily by millions.
Geno Germano, head of Pfizer's specialty care and oncology business, said Xalkori's development shows Pfizer's core research operation has bounced back.
After successes including Lipitor, antidepressant Zoloft and impotence pill Viagra in the 1990s, Pfizer's in-house scientists have had a string of high-profile drugs fail in patient testing in recent years. That's forced the company to acquire many new drugs through acquisitions and licensing deals.

Information on Mom's positive test for the ALK gene mutation of her cancer

This is great nes news- the generic name is Crizotinib, but you will see it listed as Xalkori. Anyway, it is a very promising drup and people have become no evidence of disease after taking this form of targeted therapy!!! Keep praying!!!   -Nessa

FDA NEWS RELEASE

For Immediate Release: Aug. 26, 2011
Media Inquiries: Erica Jefferson, 301-796-4988, erica.jefferson@fda.hhs.gov
Consumer Inquiries: 888-INFO-FDA

FDA approves Xalkori with companion diagnostic for a type of late-stage lung cancer
Second targeted therapy approved with a test this year

The U.S. Food and Drug Administration today approved Xalkori (crizotinib) to treat certain patients with late-stage (locally advanced or metastatic), non-small cell lung cancers (NSCLC) who express the abnormal anaplastic lymphoma kinase (ALK) gene.

Xalkori is being approved with a companion diagnostic test that will help determine if a patient has the abnormal ALK gene, a first-of-a-kind genetic test called the Vysis ALK Break Apart FISH Probe Kit. It is the second such targeted therapy approved by the FDA this year.

This ALK gene abnormality causes cancer development and growth. About 1 percent to 7 percent of those with NSCLC have the ALK gene abnormality. Patients with this form of lung cancer are typically non-smokers. Xalkori works by blocking certain proteins called kinases, including the protein produced by the abnormal ALK gene. Xalkori is a pill taken twice a day as a single-agent treatment.

“The approval of Xalkori with a specific test allows the selection of patients who are more likely to respond to the drug” said Richard Pazdur, M.D., director of the Office of Oncology Drug Products in the FDA’s Center for Drug Evaluation and Research. “Targeted therapies such as Xalkori are important options for treating patients with this disease and may ultimately result in fewer side effects.”

Xalkori’s safety and effectiveness were established in two multi-center, single-arm studies enrolling a total of 255 patients with late-stage ALK-positive NSCLC. A sample of a patient’s lung cancer tissue was collected and tested for the ALK gene abnormality prior to study enrollment. The studies were designed to measure objective response rate, the percentage of patients who experienced complete or partial cancer shrinkage. Most patients in the studies had received prior chemotherapy.

In one study, the objective response rate was 50 percent with a median response duration of 42 weeks. In another, the objective response rate was 61 percent with a median response duration of 48 weeks.

The FDA based its approval of the Vysis ALK Break Apart FISH Probe Kit on data from one of the studies.

Xalkori was reviewed under the FDA’s priority review program, which provides for an expedited six-month review of drugs that may offer major advances in treatment or that provide a treatment when no adequate therapy exists.

Xalkori is being approved under the FDA’s accelerated approval program, which allows the agency to approve a drug to treat a serious disease based on clinical data showing that the drug has an effect on an endpoint that is reasonably likely to predict a clinical benefit to patients. The program is designed to provide patients with earlier access to promising new drugs, followed by further studies to confirm the drug’s clinical benefit.

Xalkori and the companion Vysis ALK Break Apart FISH Probe Kit were approved ahead of the drug’s Sept. 30, 2011, FDA review goal date and the companion diagnostics’ Sept. 28, 2011, review goal date.

“The trend in oncology research continues towards targeted therapies,” said Alberto Gutierrez, Ph.D., director of the Office of In Vitro Diagnostic Device Evaluation and Safety in the FDA’s Center for Devices and Radiological Health. “This test is an example of the important role companion diagnostics play in determining that the safest and most effective treatments are promptly delivered to patients living with serious and life-threatening diseases.”

The most common side effects reported in patients receiving Xalkori included vision disorders, nausea, diarrhea, vomiting, swelling (edema), and constipation. Vision disorders included visual impairment, flashes of light, blurred vision, floaters, double vision, sensitivity to light, and visual field defects. Xalkori use has also been associated with inflammation of the lung tissue (pneumonitis), which can be life-threatening. Patients with treatment-related pneumonitis should permanently stop treatment with Xalkori. The drug should not be used in pregnant women.

In July 2011, FDA issued a draft guidance industry on the agency’s policy for reviewing a companion diagnostic and the corresponding drug therapy. The guidance is currently available for public comment.

Xalkori is marketed by New York City-based Pfizer. The Vysis ALK Break Apart FISH Probe Kit is marketed by Abbott Molecular Inc. of Des Plaines, Ill.

For more information:

FDA: Office of Oncology Drug Products¹

FDA: Office of In Vitro Diagnostics²

FDA: Draft Guidance – In Vitro Companion Diagnostic Devices³

FDA: Approved Drugs: Questions and Answers⁴

NCI: Non-small cell lung cancer ⁵***** 

The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.

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-Vanessa

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Lung Cancer Pill Holds Promise for those pass genetic testing-ALK Gene

Lung Cancer Pill Holds Promise For Those Who Pass Test (Crizotinib-Xalkori)

by Scott Hensley

08:11 am

August 30, 2011

From Pfizer, a drugmaker known best for medicines to treat millions, there is now a twice-a-day pill to treat lung cancer that will be prescribed for only a few thousand people each year.

The Food and Drug Administration approved Pfizer's Xalkori to treat patients with a particular form of non-small cell lung cancer, one that is marked by a genetic variation called ALK.
Only people with tumors that test positive for ALK — about 3 to 5 percent of NSCLC patients, or around 6,500 to 11,000 U.S. patients a year — are candidates for the treatment. By comparison, last year more than 45 million prescriptions were dispensed for Lipitor, the cholesterol-fighter that is Pfizer's biggest seller.

The FDA approved the pill in combination with a genetic test to detect the ALK variation to figure out who has the best chance of responding to the medicine.
The new, highly targeted cancer pill won't come cheap at about $9,600 a month. But the benefits for those with the ALK-positive cancers appear to be substantial. Half or more of patients in the studies cited in the FDA approval responded well to treatment with Xalkori. Their tumors shrank or disappeared.

But there are no definitive data so far on whether the drug extends life, though that's expected to be the case. The FDA approved the drug quickly, under a priority review approach reserved for drugs that have special promise. Pfizer has to perform more studies of the drug to confirm the agency's assessment of Xalkori.

Common side effects from Xalkori include vision problems, nausea and diarrhea. More rarely, in less than 2 percent of cases, patients experienced life-threatening inflammation of the lungs.
One high-profile patient who took Xalkori in clinical trials is former Microsoft engineer Andy Hill, a state senator in Washington. Diagnosed with NSCLC in early 2009, he started taking the pill in October of that year. Since Feb. 2010, he's shown no signs of lung cancer. "It's pretty miraculous," he told the Redmond Reporter. "I am doing things I never thought I would ever be able to do again."
For more on Hill's case and how cancer patients can make the best use of the Internet and medical professionals in making treatment decisions, watch the video below of Dr. Jack West, a lung cancer specialist at Seattle's Swedish Medical Center. (Hat tip on video to Sally Church at Icarus Consulting.)

-Vanessa

So far this week

Please read the last post for the latest update with Dr's office from last thursday. As far as this week goes, mom isn't feeling too well. She has fluid building up again and will have to go get it drained (thoracentesis) again possibly tomorrow. She is in pain on the right side of her chest. As the fluid builds in the pleural space outside the lung it begins to crush the lung.

We have not been able to get the new medicine Crizotinib yet because the pharmacy did not have it and has to order it. She is checking with them everyday on when it will arrive so that she may go get it. We don't know the exact cost of it yet either, but without insurance it is somewhere around and close to $10,000 for a one month -30 day supply. That is what we were told by the doctor. Even though the medical expenses are astronomical, the fact that mom has been receptive to the chemo (for the most part) thus far and the fact that she is positive for this ALK gene, the expectations are high for the positive results from the crizotinib. It is a pill with minimal side effects. Please God let this work on her and make her no evidence of disease!!!! We are all hopeful and praying!!

Thank you all. If you have any questions or concerns please feel free to ask and post them. Thanks.

-Vanessa

The Bad, the good news, and the unknown.

Well, the CT scan results were good and bad, but more bad than good. However, now we have an opportunity for great. I will explain, but I wanted everyone to know that there is a possible, very positive outcome in all this first.

So, we were sitting in the room and the Physician Assistant came in looking VERY grim and started reading all the results of the scan. He said there’s good and bad. He said: the bad is you have a tumor next to your heart and it is growing minimally. The pleural wall thickening has increased also. The good is that the tumors in your right lung have decreased in size. You won’t get any more chemo because Six rounds is the limit for you and it doesn’t look like it is working well enough anymore. The tumor and thickening that have grown may be a different mutation of the cancer or a different type. The cancer travels through blood and that is how it metastasizes (moves around in the body and attaches itself there).

It was very traumatic and difficult to hear. So, I immediately asked the PA about the genetic testing that was done on the fluid in her lungs (that had the cancer cells in it- the testing is done for the purpose of targeted therapy) <Side Note: I have asked every meeting with PA since July when it was done. Results came in August when they switched doctors on us and then the results were ‘lost’, but at the last appointment I asked again and he said he would personally find them>, the results were in the chart and it found that she was positive for the ALK Gene. However, it was a partial mutation. I don’t know what that means yet because I don’t have a copy of the results. I will ask for them. Anyway, this is good news. Once the PA and Doctor saw the  results of this they became so excited for my moms future and what this means. They were so giddy and practically dancing over finding out that she had this ALK gene. The FDA recently pushed to pass a drug called Crizotiib that is targeted for this ALK gene. The difference means that where Chemo works 30% this pill drug with minimal side effects works 70% results. Only 5% of lung cancers have this ALK gene mutation. It is incredibly rare.This is amazing that she has it. It is unknown territory, but this is great. It is positive. It is good news. We now have another chance at beating this disease!! She can heal with our prayers!! Everyone must believe this and believe in God's will and understanding.

It is so easy to fall into a dark place of the hopelessness and helplessness that is felt when you are dealing with cancer. We all must stay positive and remember our faith and believe in God's healing power. Pray with me.... us.....

I pray that she will become No Evidence of Disease (NED). God please continue to heal her physically and emotionally. Be with her always and let her feel your strength and goodness. Help her to know that she is not alone and that we all support her. Please God Bless her soul, forgive her for any wrong and misgivings, absolve her of all her sins. Please lord be with her. She is so good and amazing and we need her presence in our lives. Please Lord be with us and hear our prayers. Amen.

God, I ask you to heal her. I love her so much and I am not ready for any more bad news. I know that is selfish of me, but I ask you to please heal her. She is one of your vessels and I appreciate that, but please let her be a learning experience and heal her. Thank you for all that you have done. I know you are with us and I appreciate your kindness and your help in everything that you give us. Thank you. Amen.

-Vanessa

Nervous about CT Scans tomorrow

Well, tomorrow Mom gets more CT scans at 3pm. Mom is a little nervous and anxious. It hard waiting to get the results. We just pray that the scans show the tumors gone! I know God is healing her and please lord, please don't show anything on those and please do show that the tumors are gone. Amen.

We appreciate all of your prayers. Please continue to pray with us this week as we get the results on thursday. Thank you and God bless.

Realizing she is physically not up to her usual strength is tough this week

Mom, is okay but this week has been a little tough. She had her round six chemo treatment a week ago last Thursday and I think it actually wiped her out the most of all of them. She was definitely more fatigued and suffered from exhaustion longer this time. She was pretty much out of it last weekend and just rested. She told me that Tuesday was a really rough day for her and that the people in the child support court (basement of court house were extremely helpful to her). She is still going to work to help keep her mind off things and of course there are lots of bills to pay so she actually has to work. Anyway, she almost passed out from the nausea and effects of the chemo, but her friends and colleagues were there to help and she is extremely grateful. The rest of the week went alright, but by the time she got home at the end of the day she was exhausted. This weekend she has been picking up around the house and has been vacuuming and it is definitely harder for her physically as well as emotionally because she realizes that she is not as strong as she once was. It was very difficult, but she is stronger than she realizes too!!! Her physical strength will come back as well.

On tuesday we go for more CT scans and the Dr's appointment is next thursday. I will keep you informed on the results.

Thank you.

Round 6 done and still feeling the side effects

Well, on thursday mom had round 6 chemo and she has been doing pretty well, but it did take quite a bit out of her. She has been feeling the fatigue and nausea pretty hard. Other than that she is doing well and staying positive. Hopefully this weekend will be relaxing and rejuvenating.

Keep her in your prayers. We will meet with the doctors again in a couple weeks and start a new maintenance program. We will keep you all informed on the progress. God bless!