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Great news for a subset of lung cancer patients — The FDA has approved Xalkori (crizotinib). Rob’s participation in the clinical trial contributed to the data submitted to the FDA. While Rob is ALK positive, he only had about a 16 week response before progression – well below the median of 42 weeks. Why? That’s one of the big questions for molecularly targeted therapies — each individual is different. We’re hoping that AUY922 from Novartis, another new targeted drug, will prove more effective for Rob.
Dr. Jack West, an oncologist at Seattle’s Swedish Hospital, who also heads GRACE (Global Resource for Advancing Cancer Education), has written an excellent summary and analysis of the announcement.
August 26, 2011 04:54 PM Eastern Daylight Time
U.S. Food And Drug Administration Approves Pfizer’s XALKORI® (crizotinib) As First And Only Therapy Specifically For Patients With Locally Advanced Or Metastatic ALK-Positive Non-Small Cell Lung Cancer
XALKORI Underscores Importance of Molecular Testing in NSCLC and Marks New Milestone in Personalized Medicine
Significant Tumor Response Observed in Prospectively Identified Patient Population
First New Drug Approved for Lung Cancer in the U.S. in More Than Six Years
NEW YORK–Pfizer Inc. announced today that the U.S. Food and Drug Administration (FDA) has approved XALKORI® (crizotinib) capsules, the first-ever therapy targeting anaplastic lymphoma kinase (ALK), for the treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) that is ALK-positive as detected by an FDA-approved test. The effectiveness of XALKORI is based on objective response rates (ORR) and, as XALKORI received accelerated approval from the FDA, Pfizer is conducting post-marketing clinical trials to further evaluate its clinical benefit.
“Overall, lung cancer is responsible for more deaths each year worldwide than any other type of cancer. XALKORI is an advance in the treatment of this devastating illness, providing a new therapeutic option for a subset of patients with the disease,” said Ian Read, president and chief executive officer of Pfizer. “The acceleration, collaboration and critical focus of the XALKORI clinical development program reflect Pfizer’s Precision Medicine approach to advancing our pipeline and strengthening our innovative core to deliver medicines that matter most.”
Aligned with the FDA’s latest guidance on targeted therapies and companion diagnostics, the Company worked closely with the FDA and partnered with Abbott Molecular’s business in Pfizer’s clinical studies to ensure the simultaneous review and approval of XALKORI along with a diagnostic test, Abbott Molecular’s Vysis ALK Break Apart FISH Probe Kit, to identify presence of the ALK fusion gene. The simultaneous approval of XALKORI in parallel with Abbott Molecular’s ALK FISH Test marks the first time a Pfizer oncology drug or any lung cancer medication was developed and approved in parallel with a diagnostic test.
XALKORI is available immediately through a number of specialty pharmacies. Patients prescribed XALKORI can call 1-877-744-5675 for assistance accessing the medication. For more information about the FDA-approved ALK test, call (855) TEST-ALK (837-8255).
“By truly understanding the underlying genetic drivers of NSCLC, such as ALK, we can select patients who are more likely to respond to treatment. XALKORI provides a model for how to approach future drug development and cancer care,” said Dr. Paul Bunn, professor of medicine and the James Dudley chair in cancer research at the University of Colorado, Denver. “XALKORI, the first new drug approved for lung cancer by the FDA in more than six years, represents a paradigm shift in NSCLC treatment, where we’re moving away from a one-size-fits-all approach to biomarker-based treatment decisions.”
In the clinical trials for XALKORI, the study design required patients’ tumors to prospectively test positive for the ALK fusion gene biomarker, increasing the likelihood of response to the treatment. This method, a first for a lung cancer therapy not yet on the market, allowed researchers to observe a strong efficacy signal in a selected patient population.1 Preliminary epidemiology suggests that approximately 3-5 percent of NSCLC tumors are ALK-positive, translating to approximately 6,500 to 11,000 NSCLC patients in the U.S. each year. 2,3,4,5,6,7,8,9,10
“XALKORI represents a new chapter in personalized therapy for lung cancer, enabling physicians to provide the right treatment for the right patient,” said Dr. Mace Rothenberg, senior vice president of clinical development and medical affairs for Pfizer’s Oncology Business Unit. “The development of XALKORI – from publication of the discovery of the ALK fusion gene in NSCLC to FDA approval in just four years – is a remarkable feat in the oncology world and reinforces the importance of collaboration among academic research, pharmaceutical, diagnostic and regulatory organizations.”
Using a targeted approach in the XALKORI registration trials, ORR of 50 and 61 percent were observed in patients with advanced ALK-positive NSCLC.1
“Today’s approval of XALKORI underscores the important role of molecular biomarkers in cancer treatment,” said Dr. Joan Schiller, president of National Lung Cancer Partnership and chief of Hematology/Oncology, University of Texas Southwestern Medical Center. “We strongly encourage lung cancer patients to talk to their oncologists about molecular tumor testing. By having a full understanding of the molecular biology of their tumor, patients and physicians can make well-informed treatment decisions.”
New Drug Applications for crizotinib have also been filed by Pfizer with the Japanese Ministry of Health, Labour and Welfare, the Korean Ministry of Health, the European Medicines Agency and the Swiss Agency for Therapeutic Products.
XALKORI Clinical Data
The FDA approval of XALKORI is based on data from 255 patients with locally advanced or metastatic ALK-positive NSCLC across 2 multi-center, single-arm studies, including a Phase 2 study (PROFILE 1005) and a Part 2 expansion cohort of a Phase 1 study (Study 1001).1 The primary efficacy endpoint in both studies was Objective Response Rate (ORR) according to Response Evaluation Criteria in Solid Tumors (RECIST). Response was evaluated by the investigator. Duration of Response (DR) was also evaluated.1
In PROFILE 1005 (n=136), based on investigator assessments, the ORR was 50 percent, including one complete response and 67 partial responses.1 The median duration of treatment was 22 weeks. Seventy-nine percent of objective tumor responses were achieved during the first 8 weeks of treatment. The median response duration was 41.9 weeks.1
In Study 1001 (n=119), based on investigator assessments, the ORR was 61 percent, including two complete responses and 69 partial responses.1 The median duration of treatment was 32 weeks. Fifty-five percent of objective tumor responses were achieved during the first 8 weeks of treatment. The median response duration was 48.1 weeks.1
The most common adverse reactions (≥25 percent) across both studies were vision disorder, nausea, diarrhea, vomiting, edema and constipation.1 Grade 3 or 4 adverse reactions in at least 4 percent of patients in both studies included ALT increased and neutropenia.1
ABOUT XALKORI(®) (crizotinib) Phase 3 Clinical Trials
As part of its post-marketing requirements, Pfizer continues to evaluate XALKORI in confirmatory, randomized, open-label Phase 3 trials. PROFILE 1007 compares the efficacy and safety of XALKORI with standard of care chemotherapy (pemetrexed or docetaxel) in patients with previously treated advanced ALK-positive NSCLC.11 Profile 1014 compares the efficacy and safety of XALKORI to pemetrexed/cisplatin or pemetrexed/carboplatin in previously untreated patients with advanced ALK-positive non-squamous NSCLC.12
About Non-Small Cell Lung Cancer
Worldwide, lung cancer is the leading cause of cancer death in both men and women.10 NSCLC accounts for about 85 percent of lung cancer cases and remains difficult to treat, particularly in the metastatic setting.13,14 Approximately 75 percent of NSCLC patients are diagnosed late with metastatic, or advanced, disease, where the five-year survival rate is only 6 percent.15,16
About Pfizer’s Patient Assistance Programs
[One month of XALKORI will reportedly cost $9600 per month!]
Pfizer is committed to helping eligible patients prescribed XALKORI gain access to the medication, and offers the Pfizer First Resource® Program to facilitate this process. The program will connect eligible insured patients to specialty pharmacies for reimbursement support services and to obtain their medicines. For uninsured and underinsured patients, the program will provide eligible patients with free medicine. We have also developed a co-pay assistance program for eligible privately-insured patients. Patients who need assistance should call First Resource to determine whether they qualify (1-877-744-5675), or visit www.XALKORI.com to learn more.
About XALKORI(®) (crizotinib)
XALKORI is a kinase inhibitor indicated for the treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) that is anaplastic lymphoma kinase (ALK)-positive as detected by an FDA-approved test. This indication is based on response rate. There are no data available demonstrating improvement in patient reported outcomes or survival with XALKORI.1 XALKORI blocks signaling in a number of cell pathways that are believed to be critical for the growth and survival of tumor cells, which may lead to stabilization or regression of tumors.17,18 Alterations in the ALK gene are believed to be a key driver of tumor development in cancers like NSCLC.19 Although ALK is known to occur more frequently in patients with non-squamous cell carcinoma and histories of light or non-smoking, it has also been identified in smokers and in patients with squamous cell carcinoma histologies.20 Alterations in the ALK gene can occur independent of age, gender, ethnicity and smoking history.2
XALKORI has also demonstrated inhibition of the c-MET receptor tyrosine kinase and is under investigation.19
We left Mill Valley early Monday morning to drive to LA for Rob’s afternoon CT scan — the last test (or so we thought) before his first infusion on Wednesday. The drive was uneventful, and we arrived early enough to check in at Damon’s house before going to the UCLA medical center. The CT went smoothly, but then we received a call from Lisa, the clinical trial coordinator, telling us that they weren’t able to get biopsy tissue from Kaiser — a requirement for entering the trial. Evidently all the tissue from Rob’s initial three biopsies had been used up. Argh! UCLA radiology was able to schedule Rob for a biopsy on Tuesday — so much for our plans to do some sightseeing on our day off. Needless to say, Rob was not so happy with having to get the big needle again, but the procedure went smoothly and the doctors and nurses couldn’t have been better.
With all the prerequisites completed, Rob received his first AUY922 infusion yesterday. Although the infusion itself only takes one hour, there was blood work, an initial ECG, and a visit with Dr. Garon to be completed in the morning.
With any clinical trial, there is a protocol that has been developed by the trial sponsor, in this case Novartis. The protocol defines in great detail what procedures and tests must be done by the participating organization (UCLA). After the initial dose of AUY922, Rob was required to have blood and an ECG taken every hour for 5 hours, so we didn’t leave the infusion center until nearly 7pm. However, the wonderful nurses made the time go by quickly with their humor. In particular there was a giant zucchini dressed up as a patient, and that led to some fun with The Woodchuck (family joke). Our furry mascot was even presented with a knit cap and his own mini bag of ‘AUY922′, which we collectively dubbed Woodchuckinib. Laughter truly is the best medicine!
This morning we went back to the infusion center for a blood draw and ECG, as we will do tomorrow morning before driving home. Next week Rob will fly down and back on Wednesday for his second infusion. So far, Rob’s only side effect is fatigue, but the trial’s disclosure statement lists the following primary side effects: visual disturbances (83%); diarrhea (87%); and fatigue (43%). So we have a stock of immodium ready just in case…
A few other notes of interest about the trial from our consent/disclosure form:
- A total of 110 subjects with advanced non-small cell lung cancer will participate in this Phase II trial at 20 centers in the US, Europe, and Asia.
- UCLA plans to enroll 6 people. Rob is # 4, so our timing was good. We met UCLA’s first enrollee yesterday, a very nice man who is doing well after 15 weeks of treatment.
- Participants will continue to receive the drug as long as the cancer remains under control and the treatment is tolerable.
That’s all for now – we may hazard driving around Hollywood this afternoon.
There’s fortunately nothing new to report from the cancer-fighting trenches. I am enjoying good health and leading an active, full life. Fifteen and a half months into this ‘adventure’ I am in better shape now than when I was diagnosed! Crizotinib has given me a new lease on life, and I hope this amazing new experimental drug will keep working (the trial has been going on two years now, and some patients have been on the drug from the beginning with no side effects). Time will tell.
We recently had a wonderful five-day visit with my mother and sister, who hit the weather window just right. As soon as they went back to New England, the rain and cold came back with a vengeance — it even snowed on Mt. Tam last weekend! The big highlight of their time here was going to Stanford with us, meeting Dr. Wakelee and some of the staff, and getting the good news in ‘real time’ from the latest CT scan. While down at Stanford, Marnie and Leslie walked around the campus and were surprised to find my grandfather’s name on the wall of the Hoover Tower! Philip S. Platt, or ‘Pooh’ as we affectionately called him, was part of Hoover’s Commission for the Relief of Belgium during WWI, and an associate and friend of future president Herbert Hoover.
Rob, Marnie and Marge atop the Marin Headlands.
Hiking to Dad O'Rourke's bench on Mt. Tam.
John, Rob, Marnie and Jo Ann at O'Rourke's bench.
The view from O'Rourke's bench.
Other activities included a trip to our favorite museum, the California Academy of Sciences, and of course we took Marnie on the obligatory hike on Mt. Tam. We also had a family reunion one night with my cousin Jon Moore Flanagan and his wife Jen, who recently moved from Denver to San Francisco. Our family is quite small on each side, so this is an exciting development. Leslie and I look forward to seeing more of them!
Jen, Jon, Marnie, Marge and Rob
The 60th Corinthian midwinters are history now and were, by all accounts, a success this year. Yucca made a nice comeback to finish with a 1,13 (OCS), 1,1 record for third in class for the series (see Rockskipper for pics). On Sunday, not only did Hank have 2010 Rolex Yachtsman of the Year Stan Honey and his wife Sally (a 2-time Rolex winner herself) sailing with him, but he was honored at the awards ceremony for sailing in 56 of the 60 CYC midwinters to date (and winning most of them!). Leslie and I enjoyed the day as spectators on Emmet’s power boat — very civilized!
Saturday's CYC midwinter race was cold and rainy! Rob broke out his 'retro' Line 7 white smock for the occasion.
Sunday morning -- the second day of snow on Mt. Tamalpais.
Sunday's race was postcard-perfect!
The yurt is apparently surviving the Lopez winter well, and the new Lake Coffelt is now full and overflowing. John and his 88-year-old mom Enid spent the night in the yurt at the end of January, surviving the 38-degree night by stoking the fire every few hours. Our first trip to Lopez is scheduled for the first week of April – it had better be warmer by then!
I know that’s not a word most men want to hear, but today’s CT scan showed that Rob’s tumor has shrunk by ~75%. The crizotinib is working! Dr. Wakelee cautioned us not to expect further shrinkage based on the experimental results to date. What we’re hoping for is stable disease (no growth) which will be monitored by CT scans every 6 weeks. Needless to say, we are going to celebrate tonight, and having Marge and Marnie here makes the good news even better.
Rob and I celebrated our first wedding anniversary yesterday – a year ago we weren’t sure where we would be today, so this was a truly special day. With Rob due to begin the new treatment with crizotinib on Thursday, we are extremely hopeful that 2011 will be an even better year for us.
Warmest wishes to all for a happy and healthy holiday season, whatever your celebration of choice! Festivus, anyone?
My two santas!
Yesterday was a momentous day. Rob is being moved from the Phase III trial to the Phase II trial, and he will start receiving the crizotinib on December 30th. This all happened very quickly! When Rob’s cough continued to worsen, we were able to move up Rob’s CT scan, blood tests and visit with Dr. Wakelee from next Monday to yesterday. Unfortunately, the results of the scan confirmed what we knew intuitively from the cough: the cancer is still growing despite the docetaxel. Specifically, the lung tumor has grown about 25-30% in the last six weeks, and the lymph nodes in his chest are also larger. It’s a bad news / good news situation. The docetaxel didn’t do much of anything except knock about half of Rob’s hair off his head, cause him a lot of fatigue, and put him in the hospital for two less-than-memorable days. But now he gets the new, targeted therapy – this is very good news!
Yesterday was a long and emotional day. Rob was stuck with four needles – a new personal one-day record. There was a lot of waiting around, made easier by Stanford’s fantastic hospitality. The lobby of the cancer center featured a four-piece band playing Christmas music, cookies and lattes, and the chance to hang out with Mr. and Mrs. Santa Claus and Frosty (all clinic employees, as it turned out). Rob also took advantage of the free 15-minute chair massages offered to patients in the waiting area. There are free copies of the SF Chronicle, and a nice little café just off the lobby. They certainly work hard to make the clinic experience as pleasant as possible.
Stanford's cancer center lobby on Thursday.
Rob gets a personal audience with Mr. and Mrs. Claus.
Unfortunately, Rob can’t receive his first dose of crizotinib until after he repeats the baseline tests again (bone scan, brain MRI, eye exam, etc.) despite having just been through all this six weeks ago. Assuming everything is clear with the tests, Rob will ‘go on the pill’ on December 30. This gives us two weeks to get all the tests done as well as clear up what appeared on the CT scan to be an infection in his left lung, which could be contributing to the cough. Time to get healthy and be ready for the next step!
The people at Stanford continue to impress us, too, especially Dr. Wakelee. She is mentioned in Sports Illustrated’s recent feature article about Jill Costello as her doctor and friend. Jill was an amazingly courageous young woman who battled stage IV lung cancer while coxing the Berkeley rowing team to second in the nation this past spring. She was the inspiration for the Jog for Jill event which I attended, and to which many of you generously donated. Read the article if you have the time or inclination – it will bring tears to your eyes, but is also really inspirational.
In non-cancer news, we enjoyed a nice visit from Rob’s childhood friend and next-door neighbor Katy Kavanagh on Wednesday. Katy is a Professor of Forestry Resources at Univ. of Idaho in Moscow, ID, and was in town to present a paper at the American Geophysical Union’s annual meeting. She’s also a survivor, having recently spent two weeks in the ICU at a hospital in Portland, OR, for a brain aneurysm operation that could have gone either way. Rob was very happy to catch up with Katy, and I got to hear some good stories from their childhood!
Katy and Rob in the Marin Headlands.
Katy at the entrance to Muir Woods.
Katy and Rob inside a Muir Woods redwood.
- No man is an Island, entire of itself; every man is a piece of the Continent, a part of the main; if a clod be washed away by the sea, Europe is the less, as well as if a promontory were, as well as if a manor of thy friends or of thine own were; any man’s death diminishes me, because I am involved in Mankind; And therefore never send to know for whom the bell tolls; It tolls for thee.
- John Donne, Meditation XVII
English clergyman & poet (1572 – 1631)
I haven’t been able to get those words out of my head since I learned that my friend, shipmate and cancer mentor Drake Sparkman died last Friday after a two-year battle with brain cancer. Drake, a financial consultant from Stamford, CT, was one of Jim Gregory’s best friends, and joined us on Morpheus for the San Diego-Puerto Vallarta Race in 2007 and then for the 2008 Pacific Cup. You get to know a person pretty well during 3,000 miles at sea together, and Drake proved to be not only an excellent sailor but a fine human being. We had lots in common — more than we expected at the time — and stayed in touch.
Drake was about a year into his cancer diagnosis, and doing seemingly quite well, when my own cancer was discovered. While the two cancers are different — but equally deadly — the emotions are the same, and Drake was immediately there for me with advice, encouragement, and even medical connections. Leslie and I will forever be grateful to Drake for getting his Sloan Kettering oncologist to ‘call in a favor’ with his colleague Thierry Jahan, the sought-after UCSF lung cancer guru, who agreed to consult with us. That meeting led, in turn, to Dr. Jahan’s recommendation of his former fellow, Raymond Liu, as our new doctor in the Kaiser system. Drake also put us in touch with a key doctor/researcher at NIH, as well as a friend of his who had beaten stage IV lung cancer 20 years ago and counting!
Drake encouraged me to get mad at the cancer (“Get pissed at it, laugh at it, deny it. It doesn’t own you!”)and fight back. He gave me his mantra, a quote from Winston Churchill, which I adopted — it boils down to “Never give in, never give in.” I don’t believe Drake ever did give in — ultimately, the cancer just overpowered him. It hurts like hell to lose Drake, and his passing diminishes me, and everyone else lucky enough to have known him. As a lifelong sailor (his grandfather of the same name started Sparkman & Stephens), as the Commodore of American YC this past year, an as an active member in the Storm Trysail Club and many other sailing organizations, Drake leaves behind many, many friends, as well as his wife Heather and son Tucker.
He will not be forgotten.
We have an appointment with Dr. Heather Wakelee at Stanford on Monday morning. Dr. Wakelee is a leading researcher in lung cancer and is heading Stanford’s participation in the crizotinib trial. We’re keeping our fingers and toes crossed that Rob is eligible for the trial!
Yippee!!! We just returned from Rob’s regularly scheduled doctor’s appointment and we were thrilled to learn that this morning’s CT scan shows that the cancer has continued to decrease in size! The tickle in his throat is not from the cancer – probably allergies, or hoarseness brought on by the Avastin. On top of this, Rob’s ankle is much better, and he will not have the Avastin again this round to give the ankle a bit more time to heal. So for now, chemo as scheduled on Thursday, and no consideration of any clinical trials at this time. If it’s working, don’t fix it!
Now I’m going to bore you all with a few more photos from our last trip to Lopez — these are from our drive north on Highway 101 and more specifically, our drive along the Avenue of the Giants.
Rob, the Subaru, and the Redwoods.
My destiny - ELK!
Yum! Being a vegetarian isn't so bad.
Lawrence?
We had good intentions of posting some photos to the blog while on Lopez, but alas it was not to be. We spent our time organizing the yurt, chopping wood, clearing the woods, kayaking, walking, cooking, eating, and visiting with friends – we managed to check our email occasionally, but that’s about it. The weather was lovely, very dry with some morning fog, warm days and cool nights, so we felt right at home. It was cold enough in the evenings to build a fire in the wood stove — and I’m getting used to the etched elk (Lawrence Elk or Larry Elkisson?). I actually enjoyed cooking in the outdoor kitchen which consists of a two-burner propane stove, a Weber grill, and a workspace that Rob constructed from a couple of saw horses and two old doors. With only one ice chest we shopped for food nearly every day and enjoyed our visits to several local organic farm stands for fresh produce.
Yes, Rob split all that wood!
Yurt interior.
Rob and Lawrence Elk.
A toasty yurt on a chilly night.
The hay harvest was in full swing and the fields were dotted with hay bales, cows, sheep, goats and llamas. Yes, it seems as though there’s been a bit of a llama explosion on the island as farmers have brought them in to protect their herds.
Guarding the sheep.
I could use a dentist - Chuck, do you make farm calls?
Foggy morning.
Barn swallow babies in the chicken coup.
On the cancer front, we just learned that Rob’s cancer tested positive for the ALK mutation — good news since it means that he is likely to be eligible for a clinical trial of Pfizer’s new experimental drug crizotinib. The drug is currently in Phase II and III trials and has shown remarkable success in people with the ALK mutation. Unfortunately, Rob’s cancer must progress before he can be considered for the trial – bad news / good news. And even if he’s admitted to the Phase III trial, he only has a 50% chance of getting the new drug since it’s a randomized trial to compare it to the current “standard of care” drugs.
We will know more this week on how the current treatment is working. On Tuesday Rob gets another CT scan (they’ve been doing them every 3 months) and has his regularly scheduled appointment with his oncologist. He has been feeling a cough returning, so we’re anxious to get the results of the scan, although they may not be conclusive. We have lots of questions for Dr. Liu!
