Category Archives: ALK mutations

The downstream effect of two miracles of science

My friend Dr. Tom Marsilje wears a number of hats–devoted parent, dedicated scientist, cancer patient and absolutely amazing advocate/activist.

Tom holds a special place in my heart and personal history but sometimes I have to stop and remind him; we both suffer from chemo brain, a subject he recently covered in his column for the The Philadelphia Inquirer.

He was in town briefly last week so we met for lunch and a photo op in front of Miracle of Science in Cambridge. I mean, how could we not.

Linnea and Tom: two miracles of science

Linnea and Tom: two miracles of science

After snapping our selfie we headed down Mass Ave to Flour, one of my favorite little cafes. Lunch banter was about any number of things including Tom’s relatively new role as a writer, and he noted that it makes him feel good to be really making a difference. I just looked at him incredulously before exclaiming “Dude!”

At this point I should remind you that Tom codeveloped LDK-378, the second ALK inhibitor I was on trial for. Also known as ceritinib and now marketed as Zykadia.

I then used my finger to draw an imaginary line on the table. “This” I said, “is my lifeline. And this is where I started taking ceritinib. No ceritinib and my lifeline stops right there.” And then, for further emphasis: “I am alive because of you and don’t think I ever forget that, even for a moment.”

By this point I was getting a little weepy. I went on to say that if Tom were a war hero rather than a scientist who developed a lifesaving drug for a pharmaceutical company, than his role would not be so seemingly anonymous and that he would be celebrated. But that the lack of accolades in no way diminished what he had already accomplished, which was to extend the lives of so very many ALK positive cancer patients. Including yours truly. And that I was grateful to the moon and back.

Such a tight connection between the individuals who come up with these drugs and those of us who take them. A lot of cause and effect going on there and to think that Tom and I would have the opportunity to also develop a human connection is just way, way cool. This guy had my back long before he ever met me (but must of known of my existence as an ALK+ individual). Gotta say I’ve got his back now but sometimes that just feels like hanging onto contrails as he’s jetting around with astounding energy and putting his fine intellect and experience to work as an advocate/activist for patients with advanced cancers. I feel both honored and blessed (and damn fortunate) to have him in my life.

Which leads me to this closing thought: maybe we should nave a national hug a medical researcher day. Followed by a bunch of bang up fundraising.

xo

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.

Down the rabbit hole once again

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I was off drug for seven days–a subsequent post will detail why. On day seven my brother John called and at the end of our long conversation he said ‘your voice is back to normal–you’re talking fast again’. So I was. One prominent side effect of PF-06463922 for me is that I speak more slowly. It’s as if I just can’t quite drag the words out and for some reason (maybe all that effort) my voice comes out louder too. In addition, I often sound a bit incredulous, as sentences sort of trail up at the end. It’s something that not everyone notices–my neighbors in the lofts have only known the slow speaking version of Linnea. However it is quite obvious to me, my old friends and family.

That was really sort of fun, talking fast. Better still, that evening I realized that I felt different as well. Kind of like the old me–sharper, calmer, more organized in my thinking. Clearly the drug had washed out of my system.

The next morning I started dosing again. Within forty eight hours my speech slowed and that sense of internal calm evaporated (emotional lability is a potential side effect of this drug, and was a big problem for me when I was on the higher dose).

Yesterday was one of those days that just keeps poking you with a sharp stick. This whole college application thing has been incredibly complicated and Peter let me know that some forms I was supposed to submit for his financial aid package were missing. This ramped up my anxiety as I am no longer able to retrace my steps, if that makes sense. I feel sort of like someone crossing a canyon on one of those suspended foot bridges, and as I run, the bridge falls away behind me. In other words, no easy way to go back.

My daughter Jemesii was having a bad day too, as a psych eval that she had waited a month for (and gotten up very early to go to before work) was cancelled upon arrival because the doctor had called in sick. She would have to wait yet another month for a new appointment. Insult to injury, the receptionist was rude and insensitive–someone who should not be working with a vulnerable population. This stressed me out some more.

I had an appointment at noon for a new general practitioner–someone who works specifically with oncology patients. I was super excited but didn’t know how to get to MGH West and just assumed Siri (on my iPhone) could help me find the way. Well, she couldn’t parse the difference between 40 2nd Ave. and 42 Ave, which apparently doesn’t exist. And Waltham just didn’t compute for her. I turned my car on to warm it up and noticed three lights were flashing but I decided to get on the road anyway. As I pulled out I placed a call to the doctor’s office for directions but the switchboard ended up putting me through to billing where I was on hold for almost ten minutes. That individual wasn’t able to help me but said they would connect me to someone who could–but all I got was ‘We are unable to answer the phone but you can leave a message at the tone’. Damn. I tried Siri one more time, with a little less specificity. This time she understood, I got my exit, and was almost on time.

After the appointment I looked through my vehicle’s manual to see what those flashing lights meant—next to the icon that looked like an engine it said ‘take to Toyota dealer immediately’. Well fuck.

So this morning I drop my car off at the mechanic. I had scans in Chelsea so the plan was to take the train to Boston, walk to MGH and catch a shuttle to Chelsea. As I walked the half mile to the train station in Lowell our property manager called and told me that I had mistakenly sent my alimony and child support checks rather than those for rent. Oh boy. After I boarded the train I reached for my wallet and it wasn’t there.

Sometimes a girl just has to say uncle.

So home I went. Made myself a cup of coffee to calm down/warm up again. Called Chelsea to cancel my scans and sent my scheduler an email. This is one of those moments where my own challenges feel, well, just a little too challenging. That’s code for ‘and then I feel sorry for myself’. However, it never takes me long to gain perspective. Life is hard for most, and almost impossibly difficult for some. This drug that muddles my brain is also keeping me alive. And I can’t argue with that.

Miss March

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Don’t let the title fool you—mine was merely a supporting role.

The MGH Fund puts together an annual calendar, and I was asked to pose with a slide of my tumor (!) and March’s featured star, Dr. John Iafrate. John is a pathologist at MGH and also someone who knows me rather intimately–that is, on a cellular level. Those of you who are ALK+ are probably familiar with the Break Apart Fish Probe Kit–used to identify ALK+ cancers–well, that was developed in Dr. Iafrate’s lab. My continuing survival has been based on so much luck (a lot of it of the right place/right time variety). Had Dr. Iafrate not developed that diagnostic test when he did, well, I really would be history. As it was, my ALK+ status turned three to five months left to live into eleven and counting, come April (it was ten when we took this photo last year).

Pathologists are sort of the unsung heroes when it comes to the treatment of cancer despite the crucial role they play. When I was initially diagnosed with NSCLC in 2005, I wrote a thank you note to the pathologist. My general practitioner couldn’t see the forest for the trees, and had attributed more than two years of symptoms highly suggestive of lung cancer (cough, shortness of breath, clubbing of fingers, and even hemoptysis) to adult onset asthma. Even though my diagnosis was devastating I was also relieved to finally have a plausible explanation for my symptoms and that gratitude was directed toward the pathologist.

So anyway, here’s to Mr. March and pathologists everywhere. You know us better than we do, and we couldn’t make this journey without your guidance.

 

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.

 

Love story

Day 28: for my final post devoted to Lung Cancer Awareness in the month of November I am going to talk about my superhero: Dr. Alice Shaw.

Alice and I met under what then felt like sad circumstances. It was the spring of 2009 and I was several months into my snatched from the brink of death fairy tale; aka crizotinib. As far as I was concerned (and I still feel this way), my original oncologist Dr. Tom Lynch walked on water. However, I woke up one morning only to read in the Boston Globe that Tom was leaving MGH to become the head of Yale’s Smilow Cancer Center. I was devastated and sent him a quick message saying I felt like he’d broken up with me via email. In my head I was already thinking I’d have to move closer to New Haven as I viewed my continuing survival to be inextricably linked to Tom Lynch–as an oncologist he was always on the cutting edge, having tested me for an EMLK4-ALK translocation in June of 2008, long before most of the world had even heard of an ALK mutation.

Tom replied quickly and with assurance; he had hand-picked my next oncologist and he was certain I would adore her.

I was at MGH for a long trial day (PF-02341066) when Alice introduced herself to me. We chatted for more than an hour as I had soooo many questions regarding my cancer (she was the lead investigator for PF-1066 as she was for ceritinib, the next agent I would go on trial for). She listened carefully, compassionately and answered with honesty but also great detail. The treasure chest that was my own personal medical information had finally been opened and I was smitten.

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Dr. Alice Shaw (thank you MGH The One Hundred)

So what makes Dr. Alice Shaw so special? I had some fun researching her online in order to write this post and it amused me when I’d run into something I’d written when googling Alice Shaw (I have been rather vocal in my adoration). She was honored as a caregiver at MGH’s The One Hundred celebration in 2012 and at that time I said this: “Alice is an uncommon blend of brilliance and compassion. My relationship with her has greatly advanced my understanding of lung cancer while validating my personal experience–when coping with a serious illness that validation is empowering.”

That’s sort of Alice in a nutshell. Harvard educated (B.A. biochemistry, MD, PHD) she is an associate professor of medicine at her alma mater in addition to being a clinical oncologist at Massachusetts General Hospital. She has been awarded numerous research grants and awards and on November 2nd was appointed as the inaugural incumbent of the Paula J. O’Keefe Endowed Chair in Thoracic Oncology. I was fortunate enough to be in the audience, as was Dr. Thomas Lynch, my original oncologist–he has returned to MGH in the position of Chairman and Chief Executive Officer of the Massachusetts General Physicians Organization. Dr. Jeff Engleman, no slouch himself in this crowd of crowds, gave the introductory speech and noted that Alice is simply the best at everything she does. But that she is also incredibly humble and down to earth and places the utmost importance on patient care–that she is fully invested in securing the best possible outcome for every single person she treats.

When Alice came to the podium that evening, she expressed her gratitude to all those who had supported her. Mentors, colleagues, fellows, research assistants, members of pharma, benefactors, family–including her Husband Stan and two lovely sons who were all in attendance. But she also thanked her patients.

Dr. Alice Shaw is a rising superstar in the field of thoracic cancers. I recently heard her husband Stan make the humorous comment that he knew her before she was famous. The beautiful thing is, the only way in which fame has changed Alice is she’s slightly less accessible due to demand. However, as I noted in my blog about my friend Christian, although he is no longer getting his care at MGH, she still calls to check up on him. Somehow, some way, she finds the time.

In 2012 I had this to say about my oncologist and I wouldn’t change a word today: “Alice is my super-hero. She is contributing to the future of cancer research and treatment. And she is doing her best to make sure I have a future as well.”

Love you Dr. Alice Shaw!

…..

I am the lowest common denominator when it comes to instructions/rules/general compliance etc… This post is intended to be part of a blog chain this month (along with my blogs about Christian and Diane) but I failed to list the blogs prior to and following. I shall this time, however!

Yesterday: By Craig Blower about Dave Bjork found at http://craigblower.wordpress.com

Tomorrow: By Dann Wonser about Genevieve Wonser found at http://www.dannwonser.com