Tag Archives: Crizotinib

Where the heart and science intersect

Way back in 2008, when I enrolled in a clinical trial for crizotinib (Xalkori), it was the only ALK inhibitor in the world. That meant that once it stopped working (and my oncologist stressed from the get-go that this was not a cure, but rather a respite from cancer) it was the end of the road.

One year in I began to develop resistance to crizotinib but without further options, I stayed on trial and eked out almost two more years. Then, just in the nick of time, a phase I trial opened for a second ALK inhibitor–ceritinib (Zykadia).

Of course, in my universe the individuals who develop the therapies that have extended my life are absolute superstars and I the ultimate groupie. I was given the opportunity to meet Dr. Jean Cui, who formulated crizotinib, at the Xalkori Launch in 2011 and I became her number one fangirl.

I couldn’t tell you the exact moment in which Dr. Tom Marsilje and I entered the same orbit (and nor could he, as we both have chemo brain), but he codeveloped ceritinib (Zykadia). By the time I was introduced to Tom, he was battling his own cancer and suddenly our connection became a whole lot more personal.

My friend Tom is an absolute rockstar in every sense of the word and you’d be remiss not to read this profile of him in STAT–Cancer researcher races to find a cure–for his own incurable cancer. This article hits all the high points so I’ll just provide a few more personal details.

About six weeks ago Tom was in Boston and we got together for dinner (along with our mutual friend, John Novack, of INSPIRE) at the appropriately named Miracle of Science. Obviously we should have taken a selfie but neither of us thought of it (blame it on the chemo brain). We’ll just have to do a redux at a later date.

However, the first time Tom and I met in the flesh (like so many of my friendships, ours existed in the email/social media sphere), it was entirely by accident. We were both in DC this past spring, lobbying for our individual cancers (lung and colon). I was waiting for an elevator in the basement of the Russell Senate Building and noticed a man standing with his back to me and thought ‘he sort of looks like Tom Marsilje’. Well, that man turned around, saw me, started to shake a little (we were both gobsmacked), and then I rushed over to give him a big ol hug. The serendipity of our encounter was just sort of perfect.

Anyway, count me a huge fan. Even if he if wasn’t one of the reasons I’m still here, I’d be impressed by and with Dr. Tom Marsilje.

About time

Sort of ridiculous, but my About on this site was some 4 1/2 years out of date. Whoa, good problem to have, rewriting Abouts. So, it’s been freshened up a bit. About time I might say. Little preview here (to save you from having to push that About button):

Time for a new About! The last one had me six and 1/2 years out from diagnosis, on crizotinib (Xalkori) and happily married. So much water under the bridge since then, my friends!

So, updated version. I was Linnea Duff, but I’ve been divorced since 9/1/15 and have reclaimed my birth name, Linnea Olson. I am now 56 flipping years old–old enough to qualify for a senior’s discount at Salvation Army and Saver’s thrift stores. And I couldn’t be happier. Old age is not a problem, it’s the goal!

Crizotinib bought me close to three years, but in the time since I spent 18 months on trial for ceritinib (Zykadia—where do they get these names?), returned to chemotherapy (carboplatin and pemetrexed), took a breather, returned to crizotinib and then in May of 2014, started my third phase I clinical trial for lorlatinib. Despite having acquired some secondary mutations along the way–S1206Y and G1202R–I have had both a positive and sustained response to my third ALK inhibitor.

In April, it will have been eleven years since I was diagnosed. My three kids are all adults now, at ages 31, 30 and 18. The youngest, who is in the college application process, wants to be a cancer researcher. Mama couldn’t be prouder.

And me? Living in a renovated mill in Lowell Massachusetts in a community of artists. I am once again a practicing artist and also sell vintage clothing on the side (The House of Redemption). I continue to devote a fair amount of time to lung cancer advocacy and in addition to my blog here, I write for CUREtoday.

Best news of all? I feel great, absolutely fabulous.

And I think I’ll hang onto the video—even though it is out of date. It just makes me SO happy.

Linnea live (I like the sound of that)

This video was recorded at the annual LUNGevity Hope Summit in 2014 and fits in perfectly with the theme of clinical trials. When I refer to starting a new trial, it is for PF-06463922 or lorlatanib (which has kept my cancer stable for 18 months now–woohoo!). I’m a little breathless and hoarse as my cancer was advancing again. I noticed immediately how fast I am speaking– markedly slowed speech has been a side effect of PF-06463922.

Slow, fast, hoarse or not, the most important message here is one of hope (thank you LUNGevity). When I mention going from cure to living longer I am talking about accepting the fact that I would never be cured. That’s a difficult concept to embrace but in order to make it even remotely acceptable I found I needed to replace cure with a potentially obtainable goal—becoming an outlier. At ten plus years (eleven, in April) I am there.

Secondly, the importance of options. When diagnosed in 2005, the first hurdle I hoped to jump was qualifying for surgery. I had nineteen lymph nodes and most of my left lung removed followed by four rounds of adjuvant chemo and yet my cancer returned almost immediately. Two strikes, and I’d been informed that treating lung cancer was basically three strikes and you’re out. My first clinical trial in 2008 was a long shot. I was thrilled beyond belief when I responded to crizotinib, but also understood that it represented a temporary fix and that there was nothing else out there once it stopped working.

Thankfully, that’s no longer true. Sadly, there aren’t viable options for everyone with lung cancer. Medical research got me to where I am today (alive!) but we can’t stop now.

Taking the leap into clinical trials

I was initially diagnosed with non small cell lung cancer in April of 2005. My tumor was large (5 centimeters); a poor prognosticator. However, it had not spread beyond my lungs and I was staged at IB. One week after diagnosis I had the lower lobe of my left lung removed. As I was recovering from surgery my new oncologist introduced himself; Dr. Tom Lynch. I had no idea back then, but I was incredibly fortunate to have Tom select me as a patient. The reason behind his coming to me rather than the other way around? As a young (age 45) non smoking woman, I fit the profile of someone who might be EGFR+ and Tom was an early innovator in the investigation and treatment of EGFR+ patients.

I tested negative for an EGFR mutation but in the process acquired arguably one of the best oncologists in the world; someone who was always forward thinking and cutting edge in his approach to treatment. In fact, I was offered a chance to enroll in my first clinical trial soon after surgery. Because of the size of my tumor, adjuvant chemo was indicated and a trial that would include the addition of avastin was proposed. I was having a difficult time even being convinced to have chemotherapy (Tom was adamant) and I couldn’t wrap my head around the possibility of also being a medical research subject. As it turned out I would not have been a good candidate anyway–I am a bit of a bleeder and I was coughing up blood for weeks post lobectomy (there is a small but significant increased risk of serious pulmonary hemorrhage secondary to avastin).

Fast forward to September of 2008, two months after I’d been restaged to IV and advised that I likely only had three to four months to live. At my scan review after two months of tarceva–tried as a last ditch effort even though I was EGFR-, there was nothing but bad news from the radiologist. However Tom shared that a sample of my biopsy had been submitted for further genetic screening and had come back positive for an EML4-ALK translocation (another example of how ahead of the pack he was—the ALK mutation had been identified as a driver in NSCLC only months prior to that).

As we discussed the significance of this finding we also reviewed my options going forward. The way Tom saw it, there were four possible scenarios. I could stay on tarceva, return to traditional chemotherapy, do nothing (that option only underscored how serious my situation was) or attempt to enroll in a phase I clinical trial that targeted ALK mutations such as the one that was driving my cancer.

Would you believe me if I said I never hesitated but instead leapt at the opportunity to be in a clinical trial? Why now but not back in 2005?

This is why.

This image of my scan says it all. The upper lobe of my left lung was now almost completely clouded with consolidated ground glass tumors which had spread to my right upper lobe. And I had been told that I might have three to four months to live two months ago. The math was easy—I had almost run out of time and out of the four options I’d been provided with, only one seemed to offer a glimmer of hope.

And glimmer is the operative word. There was no precedent for me back then—no reason to believe that this trial might actually prove effective. All Tom could offer me was the fact that I had been preceded by one other participant at MGH. ALK+ like me but so debilitated by disease that they were confined to a wheelchair. Their initial response had been extremely encouraging, to the point where the wheelchair was temporarily abandoned. But then they had died, in part due to the toxic effects of the trial drug on their liver.

So this is what I knew. One before me with a promising response who had succumbed both to disease and to the toxic effects of therapy. That the experimental therapy could in fact prove fatal to me as well. But that my cancer would certainly kill me if I did nothing. An easy choice, after all.

And so, on October 1 of 2008 I had my lead in dose of the drug that would eventually be known as Xalkori.

 

As it turns out, not quite enough (of me)

The word from the lab looking for the PD-1 protein in my biopsy is that there weren’t enough cells (cancerous or otherwise) for a thorough analysis. If it is determined that enough tissue was ‘banked’ after the biopsy, a sample will be resubmitted. Dr. Shaw is not particularly optimistic.

So, the plan for the moment is to watch and wait. We will rescan in November and as long as I don’t become significantly more symptomatic, my situation will be reassessed at that time. In lieu of a PD-1 antibody, I could potentially return to one of the ALK inhibitors which I previously benefitted from:  LDK378 or Crizotinib—although as the LDK is still in trial, I’m not sure how that would work. Chemo remains an option but given the slew of side effects, I would say it is the least attractive choice. What I’m really hoping is that I can hold out until the next ALK inhibitor comes to trial (rumored to be end of this year or beginning of next)—the timing could be just right for me.

In the meantime, my plate is plenty full. I’m looking for a place to live as well as a means of support. I realize that statement implies much and answers little; I’ve got a lot to process and when the time seems right, I will discuss this new chapter in my life.

Xalkori Launch

We take the stage

Alright Miss Duff. Enough procrastination. Time to write about the Xalkori launch.

From the evening of October 25th through Thursday morning on the 27th, David and I were guests of Pfizer at the Copley Square Marriott in Boston. We were in attendance for the patient portion of the Xalkori launch.

After registering on Tuesday, I located the ballroom where Alice (Dr. Shaw) was scheduled to speak. An interactive display had been installed in the foyer with patient photos and videos, and as I was checking those out I ran into the speaker herself. There was time for a quick hug before she took the stage and I slipped into a seat at the back of the room.

Alice recounted a brief history of the PF-02341066 trial to an audience of about 350 Pfizer employees; the majority of whom were pharmaceutical reps. She was joined onstage by Robert Martensen, an author and physician, who happens to have ALK+ NSLC  and who began taking Xalkori last summer. Of special note, the histology of Dr. Martensen’s lung cancer is squamous, so here is a splendid example of the old exception to the rule theory.

It was interesting to hear the dialogue between two doctors; one of whom was also the patient. At the conclusion of their presentation, we had a ‘practice’ session, and I was able to meet the other ten patients whom I would be joining for our portion of the program the following morning. All of them, (except for myself) were current participants in phases II and III of the crizotinib (Xalkori) trial and had enjoyed positive results that ranged from stable to a whopping 100% response.

On Wednesday morning the eleven of us, plus our caregivers, made a rather dramatic appearance onstage as we lined up behind a white scrim which was then dropped at our feet (the reveal!). After we were individually introduced by the moderators (hello Jonathan and Chris), our families retired to the audience.

It was a moving experience, as each patient took turns describing the impact Xalkori had made on their lives.  I found it rather an amazing vantage point as well; looking out over the sea of faces in the audience, many of whom were wiping away tears.

Each patient was given a chance to answer some prepared questions. When it was my turn, I commented that it wasn’t exactly fair that the moderators were the only ones with teleprompters, given the fact that most of us on stage had done some really hard drugs.  I also asked the audience to take a good look at the eleven hale and hearty individuals (patients) in front of them and to remember that we each had stage IV lung cancer. Given the ravages of the disease as well as the difficult side effects of most traditional treatments, our current state of health was perhaps the most amazing thing of all. Not only had Xalkori given us more time, it was quality time.

After the session concluded, we had the chance to meet some of the people behind the development of crizotinb, including Keith Wilner, Pfizer’s Senior Director of Clinical Research, and then perhaps the biggest rock star of all,  Dr. Jingrong Jean Cui, the scientist who invented crizotinib.

Dr. J. Jean Cui with some of her biggest fans

Jean is the epitome of intelligence, diligence, humility (!) and creativity. She shared with us a tantalizing glimpse of just what lay behind the synthesis of a complex molecule that would become Xalkori.

And this is it: Xalkori

Pfizer thoughtfully arranged a luncheon for the patients and their families, and we were joined by several key members of the team involved in development to market phases of PF-02341066/crizotinib/Xalkori. Possibly not your usual cafeteria chatter.

I had overheard that there would be a tribute to my friend Kevin Brumett, who was one of the very first people in the world to go on what was then know as PF-02341066. Kevin passed away in May of 2009, just a week after marrying his sweetheart, Stephanie Fellingham. With his boundless optimism, energy and generosity, Kevin touched the lives of many. In January of 2009, he had been invited to speak at the Pfizer laboratories in La Jolla, an experience he found profoundly moving. It was only fitting to close the Xalkori launch with a tribute to this exceptionally brave young man who eagerly went down what was then an unproven path.

There was time for a short and much needed break; I felt emotionally tapped out at this point. Then we crowded into buses with the pharmaceutical reps to join in a team building exercise at yet another venue. It was actually a great chance to get to talk to more people, and the product of the exercise was some lovely murals for The Lung Cancer Alliance of Massachusetts.

When finsished, we moved upstairs for dinner, and once again I enjoyed having the chance to converse with members of the crowd. An unsolicited plug for Pfizer here; I was truly impressed by both the sincerity and level of commitment exhibited by their employees. Just a really great group of people.

Just when I thought this day couldn’t be any more meaningful, Dr. Tom Lynch, my original oncologist and now Director of the Yale Cancer Center, walked up to our table. After a few moments to catch up, he took the podium, and knocked the socks off a crowd that on the third and final day of the Xalkori launch, was by all rights exhausted. Tom possesses the uncommon combination of brilliance and a real knack for performance; he is a phenomenal speaker. And his enthusiasm is absolutely infectious. And, of course, I couldn’t help but be pleased that he included the before and after image of my lungs (pre and post crizotinb/Xalkori; nice to see them on the big screen!).

The evening concluded with a moving presentation by Diane Legg and Rich Monopoli, friends and associates of mine as well as co-chairs of the Massachusetts Lung Cancer Alliance. What a day!!

Before I sign off, I would like to say how pleased I was to have people come up and introduce themselves and to say that they read my blog; I am honored. It was also wonderful to be reunited with those I’ve had the pleasure of meeting before; both filming in Meredith and on my trip to the facility in Connecticut. In closing, thank you, Pfizer, for making us feel so welcome and please, keep up all of the good work. You will never know how much it means to our friends, families, and those of us with lung cancer.

FDA approval for crizotinib and a new name: Xalkori

On Friday, August 26th; crizotinib received FDA approval. It is now called Xalkori. Nice little features on both the ABC  (scroll down to find Xalkori) and NBC evening news a couple of nights ago. That’s my oncologist/goddess Dr. Alice Shaw providing commentary, and in the NBC piece, the images of the before and after chest CT scans are my lungs (an online friend recognized them and emailed me!). They do get around (my lungs and Alice).

I should also mention that there was a story about Pfizer’s coup in the Wall Street Journal on Tuesday with a picture of and a few quotes from yours truly. My Dad Ollie, who read the WSJ faithfully, would have been pleased to see me there.

I’ve noticed some criticism on the blogsphere, as Xalkori comes with a hefty monthly price tag ($9600), but Pfizer has taken steps to provide financial aid for those who need it. Also called out has been the fact that only 4-6% (or according to this latest data, almost 10%) of people with NSCLC have a mutation of the ALK gene. However, there are so many cases of lung cancer world wide (according to WHO, 1.4 million deaths yearly from lung cancer), that when you do the math, it is a truly significant number of patients who shall potentially benefit.

So yes, Xalcori is big news for Pfizer as well as those of us with lung cancer and the FDA is to be applauded for streamlining the often ponderous approval process.

And now, on a more personal level; what’s up with me.

On August 19th I took my final dose of crizotinib (Xalkori). I am now ‘washing out’ in preparation for my next party trick (make that a miracle). Yesterday I peed in a cup, had bloodwork, a physical, an EKG, a chest and abdominal CT (with contrast–blech) and a PET scan as well. I was given one of those nifty cards identifying me as residually radioactive for 24 hours (just in case I encountered someone with a geiger counter).

I am scheduled for my lead in dose of LDK378 next Wednesday and that’s when the circus really starts.

In the meantime, I am feeling pretty crappy. I saw Alice (Dr. Shaw) yesterday, and she thinks that quite probably, the crizotinib was still conferring some protection, which is good news if in the future we want to add it to my arsenal again. Now that I’m off treatment, my energy level has really dipped and my shortness of breath is catching up to me. Today I made myself go on a walk, as I’ve been breaking my own rules lately (never stop moving). It was also Peter’s first day at the Academy, and he’s going to require a lot of support as he adjusts to a very rigorous academic schedule, so I’ve got to stay on my toes.

What can I say? It is a stressful time for all of us, but we are doing our best to stay positive and hopeful. Because that’s how it’s got to be.