Tag Archives: lorlatinib

Just a little documentary

I have now been in phase I clinical trials for two Pfizer drugs—crizotinib and lorlatinib (Xalkori and Lorbrena). A few weeks ago I travelled to La Jolla for a CNN produced documentary. Perks of this project included spending time with rock star researcher Ted Johnson as well as a tour of the Pfizer Labs. And of course anytime I get to see the sun setting over the Pacific ocean, that’s a plus as well.

As for the documentary, it speaks for itself. Give it a little gander. Pfizer, thanks for letting me represent. And for keeping me at this party.

xo

Understanding the enemy

‘When there is dust rising in a high column, it is the sign of chariots advancing; when the dust is low, and spread over a wide area, it betokens the approach of infantry. When it branches out in different directions, it shows that parties have been sent to collect firewood. A few clouds of dust moving to and fro signify that the army is encamping.’ Sun Tzu, The Art of War.

My enemy, despite heavy artillery (lorlatinib plus carboplatin and pemetrexed) continues to advance. Hence the need for another approach. On Tuesday I have yet another CT scan in preparation for the upcoming clinical trial–it will be interesting to see if the fact that I am feeling better is supported by radiographic evidence. Either way, I think it is time to surprise cancer, which has grown both in size and cockiness.

7.1 cm is not my friend. Nor is lymphangitic carcinomatosis.

Sometimes I love me some drugs

Not gonna lie. The unholy combo of lorlatinib, carboplatin, pemetrexed, MOVING has been kicking my ass. Oh yeah, and cancer. Two twelve hour one day drives to Toledo and back were not as restful as one might assume. My energy is shot, my skin is shit (long term side effects of lorlatinib not helped by the new stressors) and last night I fell to sleep just imagining that I was a baby held in some loving arms. Breast fed, not with a bottle–the route my hep fifties mom went 😉

Yep. I am spent. Second infusion is tomorrow and steroids came to my rescue today.

Nasty, nasty drug that one. Insomnia, constipation, rage. But also an unnatural sense of energy just when mine was flagging. And not one to waste an opportunity, I got a hell of a lot done today. This new little home of mine is looking just like that—a place that someone would like to come and stay awhile. Maybe hunker down a little.

Mañana mama.

xo

Rattle and roll

I was exhausted last night. Rightly so, I imagine.

As I lay in bed, I could feel the powerful impact of two different cytotoxic agents on all the various bits of me. Havoc was being wreaked, like some marauder in the garden.

I went with this garden imagery, the cancer in my lungs a persistent and deeply rooted weed. And I pictured it being torn asunder, plucked from the substrate of my flesh, shaken violently, bent, torn, limp, lifeless. Every last cell of it.

When I awakened this morning the sound in my lungs had changed in timbre. The crackle of leather had been replaced with something akin to a broken tea cup. Very fine bone china, rattling around.

Hmmm, I thought. This is an improvement. What was hidebound now feels looser, dryer, easier to dislodge.

Onward.

xo

Up and over

When titling my previous blog I had a verb in mind. An action verb.

Chemo is a wall. And–frankly–that is the point. What sucks for me hopefully sucks for my cancer as well. All those side effects are indicators that the poison is going about its nasty little business.

What I’d like to clarify is how I’m taking this. Not lying down.

This particular chemo combo is a small misery compared to what I have experienced in the past. Fifteen years ago I was given a doublet of cisplatin and taxotere. My then oncologist explained, in the bluntest terms possible, that he intended to bring me to the brink of death and then bring me back. All in the name of eradicating my cancer.

Well he was true to his word. That shit blew. And I’d start to feel the side effects before we even got home after infusion. I spent days riding out the storm in my lazy boy chair (dubbed the lazy girl). By the fourth cycle I didn’t have a hair or an ounce of extra fat on my body and I was coughing up what looked like coffee grounds.

Now that, my friends, was hell. And it gave me some perspective. A rocky baseline if you will. Added to the mix was the fact that seven weeks earlier I’d had a lower left lobectomy, not vats but rather the old fashioned way. Ribs spread, large incision. Brutal.

So this is, relatively speaking, a walk in the park. I do feel a tad crummy. But I am also going about my business. As I live alone that means walking the dog, shopping for groceries, cooking. And, because my life is in fact over the top crazy, moving.

Yes. Again. My current situation did not work out quite as I imagined. One of my closest friends understood that this had become a source of stress for me and as fate would have it, an apartment that was located directly across the street from her opened up.

It was now or never and given the possibility that I may feel worse rather than better in the future, it was a no-brainer.

So yeah. Rather than surfing the couch I have been loading and unloading boxes. Yet again. On Wednesday my friend Melinda has arranged for a moving company to take the furniture and the books. And yet another impossible task will have been accomplished. Under ridiculous yet necessary circumstances.

I share this all so that others understand that even though chemo is undeniably unpleasant, it is also doable. This is an important concept for those who have only been on targeted therapies, and who are loathe to consider chemo, because of its bad rap.

In my case, I have a clear and unwavering agenda. It’s this: I really want to live. And I am willing to scale a million walls in order to do so.

Who knows. Maybe chemo works better if you’re not laying on a couch. I kinda doubt anyone has done any research around physical activity post infusion.

Consider this a pilot study.

xo

Scaling

I have hit the wall that is week two. Massive fatigue. Rheumy eyes. Gums that weep, a mouth that feels like sandpaper. Nosebleeds.

Loose of bowel, I’ve lost five pounds. Neuropathy is both afoot and at hand.

Numb and bloody. Edges and corners raw. But alive.

Alive, alive, alive.

And happy about it.

I had the thought that this is what cancer reduces existence to. Gratitude even in misery. But then I rethought that thought. And this time it came out this is what cancer elevates existence to.

How fucking fantastic is that. This, my friends, is unconditional love. Life, so treasured, that even when it’s all a bit raggedy it remains sought after. Beloved. Adored. Precious.

Something worth fighting for.

xo

Oh girl

I think I got this.

I drove myself to and from the hospital yesterday. No problemo. Early morning breakfast with my daughter, and then an appointment with a neuro onc. Two weeks ago I started getting this very brief and yet excruciating pain on the top of my head. It lasts seconds, is intermittent and unpredictable in onset, but is always in the exact same place. And it stops me in my tracks.

My first thought was an unusual presentation of shingles. But given that I am a cancer patient one must always rule out other possibilities. My exam demonstrated decreased sensitivity on the left side of my body, top to bottom. My brain MRI’s have been positive for multi infarcts for some time now (little strokes) and a slightly larger stroke is a possibility. As is–the highly unlikely–scenario that I have a tumor or some other structural impingement. This finding is seemingly unrelated to the pain on top of my head which could be trigeminal neuralgia or maybe even just some weird neuropathy. At any rate, I’ve not had a brain MRI for a good long time now and so one is scheduled for the 19th, when I receive my next chest CT scan. This will necessarily be with contrast, but evidently better contrast than before.

After that I was joined by my friend Jenny Ro, who you’ll hear more about later. I met her while I was preparing for my TED talk and we just immediately clicked. She was gracious enough to offer to be my chemo buddy yesterday. My son Peter joined us for a couple of hours as well, lending an almost festive feel to the affair.

First up was scan review, and it was as I expected. Overall progression. Not rampant but persistent. Alice said she was glad we’d decided to begin treatment.

And then, up to the eighth floor and infusion, where I was immediately recognized by a phlebotomist. That’s what happens when you’re a lifer. Some saline, ten minutes of carboplatin, more saline and then thirty minutes of pemetrexed. In and out.

It was necessary to stop at the pharmacy as I was out of ativan and needed some scrips for anti emetics as well. And some tortilla chips to go with the guac I’d stocked up on the day before. That, some cut fruit, and turmeric milk all went down nicely.

I slept like a baby, waking once in a cold sweat with tears all over my face. No idea why.

Today I am feeling a little bit more like I’ve been run over by a truck, but again, all manageable. Alice texted me and I said that if I continue to feel ok, then next time I’d like to consider ramping up the carbo dose. Of course, I have a scan prior to that, so if it’s not doing anything, I suppose there is no point. But my fervent hope is that it is.

This girl. This girl wants to live.

Action plan

I had an oncology appointment in Boston today and met one of the new members of my team. Alice will remain my oncologist, but her role will necessarily be more limited than before. I told this new doctor that I felt my cancer was now in my right lung as well–I can both feel and hear it (wheezing/crackling). She took a listen with the stethoscope and confirmed.

So those horses are not only out of the barn–they are moving to another pasture.

Obviously that’s not a good thing. It’s a damn shame that lungs are an essential organ, but it is what it is. And what it is, is that it’s getting harder to breathe.

Time to spring into action. Given the fact that I have some upcoming big plans (a panel at Takeda, my TED talk, birthday, Thanksgiving) we are holding off until December. Scans on the 2nd, first infusion on the 5th.

Originally the plan was to add carboplatin and avastin to lorlatinib. However I have already had four rounds of carbo as well as four rounds of cisplatin. A lot of platinum for one girl. My peripheral neuropathy is rather severe, particularly in my feet. On various occasions I have walked around unaware that I had cardboard liners, stones, or wet socks in my shoes. The bottom of my feet are almost totally numb, and although I have adapted to this unsettling scenario (only an occasional stumble) we certainly don’t want it to get worse.

So Alice felt carbo was not the best bet, and that perhaps we should go with pemetrexed instead. We were going to add avastin, in the hope of hitting the cancer with a bigger hammer. However, I have been coughing up some blood and also have had small abrasions become larger wounds that were loathe to heal–both indicators that I might be at greater risk for bleeding in my lungs secondary to avastin.

There is a distinct possibility (and a big, big hope) that chemotherapy will have a synergistic effect with both lorlatinib and binimetinib–the drug I would receive in conjunction with lorlatinib in the next clinical trial I shall enroll in. Given that, I want to make certain our approach is not tepid. As avastin has been ruled out, I asked that carbo be added back in–but at a lower dose. If I tolerate the first round, we will continue. If not, then it will simply be pemetrexed.

I had a vitamin B12 shot today and will begin taking folic acid in preparation for infusion. I am ready but also understandably leery. This will be the first time that I have undergone chemo while living alone. That in itself should be a bit of an adventure. However, I think I know what to expect.

And I am ready to launch an attack.

Climbing trees

I have no fear of heights and I love to scale things. Trees in my youth, some rock climbing in my twenties, scaffolding and the coupling of freight trains in my fifties.

Well, it would seem I’ve circled back to trees and this time I am way out on a limb.

I had my routine scans last Friday. Afterward I texted Alice to let her know I was certain they would show progression, based on my physical symptoms. My scan review was to be this Thursday with my nurse practitioner rather than Alice and I wanted to make certain the two of them talked options prior to my visit.

After Alice had a chance to review my scans personally, I received a text from the Goddess herself. ‘Just wanted to chat. Thanks.’ Alice has been my oncologist for more than eleven years now. I can read between the lines with relative ease and I knew that if my assertion was incorrect–that my scans had in fact showed stability–a reassuring text would have sufficed.

I had a dry run for my panel yesterday morning and Alice was tied up in meetings so it would be quite a few more hours until we had a window in which to speak. Back in the day this would have undone me but years of living with this situation have lent me a certain calmness.

Our conversation was brief but confirmed that my scans do indeed show progression. Likely more troubling to Alice are my cough and the accompanying wheeze from my left lung.

My Thursday scan review has been moved to Friday, and I will meet with Alice rather than my nurse practitioner. We will discuss possible options as well as timing. It all feels a bit like firing a gun with an empty chamber.

And yet I know Alice will come up with something–likely combining lorlatinib with some other therapy. I will keep my ship pointed toward the shore. Hope is not cheap but I have made more out of less.

xo

IASLC 2019 World Conference on Lung Cancer

So it gets better. Not only did I travel to Italy this summer, I also attended the 2019 World Conference on Lung Cancer in Barcelona, serving on a group panel addressing ways to improve clinical trials, along with my peer/good friend Janet Freeman Daly.

Janet is a scholar among advocates/activists and she presented compelling data. My territory is the more emotional piece, pulling on years of boots on the ground experience. I had no slides. My speech was written the night prior to our panel. I would imagine there was no presentation even remotely similar at this conference with 7500 attendees.

Of course, I was preaching to the choir as almost half of the people in the room were fellow advocates. Ideally, this message would reach a broader audience (I’m shooting for the plenary session next year). As it was, I received a standing ovation, some tears, quite a few hugs. And requests that I share my speech online, so folks, here it is.

*And no, I’m not a doctor. But I was tickled to be called one.

What would you do to stay alive?

Chances are, almost anything. 

If, as I was, you were diagnosed with lung cancer at the age of 45, you might have most of one lung removed, not by vats, but rather a good old fashioned lower left lobectomy, followed by four rounds of adjuvant chemo—a notoriously nasty doublet of cisplatin and taxotere. 

You would do these things because of your husband, your children, your parents, your siblings. You would do these things because the youngest of your children has not yet turned eight. You would do these things because, at 45, there is so much left undone. And you would do these things because you don’t just like life, you love it.

That desire to live might not diminish even as your cancer returns and metastasizes to your right lung. You might well hang onto hope right up until the moment you ask if it is time to get your affairs in order and the answer is yes—best guess, three to five months in which to do so. 

Dazed acceptance takes the place of desire as you say your goodbyes. And then something quite unexpected happens. You learn that the re-staging biopsy revealed that your cancer is positive for a newly identified oncogenic driver in lung cancer, an EML4-ALK fusion. 

By chance there is a phase I clinical trial for an ALK inhibitor at the very hospital where you receive your treatment. One other person has enrolled but quickly died, in part from side effects from the experimental therapeutic. 

You know that you are also dying. However, on this day you discover that you have not lost hope. The trial is a long shot but maybe, just maybe, it will extend your life by several months. Your greatest anxiety is that your decision to enroll may hasten your death. But you can’t not try, and so you do.

You end up being the 4th person in the world with non small cell lung cancer to take the first ALK inhibitor. 

Eleven years and two more phase 1 trials later, you are still alive. You have lived long enough to see your youngest graduate cum laude from Phillips Exeter Academy. In two weeks, he will enter his fourth year of study at MIT.

In November you will turn 60, and your oldest child 35. None of this was imaginable. None of this would have happened without both the opportunity as well as your personal decision to enroll in clinical trials. 

Your life is full and you feel abundant gratitude in regard to your good fortune. You are aware that for many, your continuing survival is a miracle.

However, you know differently. This was no miracle. It was a combination of medical science and much blood, sweat and tears. 

I succinctly describe my clinical trial experience this way: it has been my privilege and my burden. 

Since October 1 of 2008, I have spent more than a decade as a participant in clinical trials. First in human, early cohorts, all of them. Each time I’ve had approximately a 70% resolution of my cancer and all told, six years of stability. My quality of life has  been, for the most part, extraordinary. However, that is not to say there have been no side effects. Most have been manageable, but some have been extreme, from liver toxicity to cognitive deficits.  I have borne these and not let them get in the way of an incredibly full life. However, the challenges are not to be minimized. 

Every year I max out my deductible in January. Many are under the impression that clinical trials are free—in the trials I have been in, drug has been provided by the sponsor as well as the cost for occasional procedures—for instance, echocardiograms in my current trial. All other medical procedures have been billed to my insurance, which means I am paying the copay. And the non medical expenses—travel, lodging, meals, parking—have all come out of pocket. My pocket. 

Trials are time consuming—consuming in general. My marriage of 24 years ended six years ago—in large part because my then husband found our lives too cancer centric. The financial fallout of divorce has been that my own income is limited—with far too much of it allotted to my medical care.

The emotional burden of the ups and downs of literally living while dying has taken its toll on not just me, but my three children. Uncertainty has a permanent place at our table. 

And then there are the astounding number of scans I’ve undergone—not because they were clinically indicated but rather because they were mandated by the one size fits all protocol of clinical trials. To wit: even though my cancer, invasive mucinous adenocarcinoma, is confined to my lungs, I have now had sixty abdominal CT scans, ten of which were PET. More than one hundred spiral CT scans of my lungs, ten of which were also PET. 42 Brain MRI’s. And sundry x-rays, bone scans, full body PET scans in addition. This in an individual with highly mutable cells. 

Several years ago I requested that the scanning schedule be amended from every six weeks—not standard of care—to every three months. Not just for me but for every participant who had been enrolled for twelve months or longer. And that attention be paid to individual diagnoses. That someone such as myself, with no brain METS, should not be required to undergo such frequent brain MRIs. Keep in mind that in addition to being exposed to unnecessary radiation, I paid copays on those 60 abdominal CT scans and 42 brain MRI’s. 

When my request was ignored by the sponsor, I made the risky decision to become noncompliant, refusing to have anymore abdominal CT scans and also declining injected contrast with MRI’s of my brain, as I was concerned about the possibility of gadolinium retention. Sadly, a year later my MRI was in fact positive for gadolinium—what is referred to as a brain stain, so I now have heavy metal in my cerebellum—a finding with poorly understood consequences. 

Oddly, there has been a push to humanize the role of clinical trial participants, by euphemistically referring to them as partners. As I have written in a blog titled ‘Don’t call me partner’, this is not a partnership of equals, and in fact, is a relationship that at times is abusive. 

That’s right. I am grateful but also angry. Angry because this potentially abusive relationship is codependent. You need me but I need you too. Desperately. 

Therefore, there is nothing to be done but to work on this. 

I would begin by suggesting that there should be some sort of bill of rights or manifesto for participants in clinical trials. A sort of contract that would acknowledge, recognize and even honor the fact that the ultimate purpose of clinical trials involving human beings is not to advance science or to enrich shareholders—it is to address human suffering brought about by disease. 

Recognize that we are not truly volunteers. We didn’t choose this course, we were chosen. A terminal illness is a terrible thing and we all understand that desperate times call for desperate measures. Clinical trials are not some extreme form of community service—we are enrolling because we are hoping that our lives shall be extended. If our contribution helps others, that is a bonus, but do not make us feel that wanting to live should be anything but our primary motivation.

Healthy ‘volunteers’ in clinical trials are almost always compensated for participation. Why? Because they wouldn’t volunteer otherwise. And yet those of us with cancer are not only not compensated, we generally pay to participate, in the form of deductibles and other out of pocket expenses. In my more than decade of participation I have never even had my parking comped, a not unreasonable expectation as more frequent visits are required per protocol. Ideally, I, like those ‘healthy volunteers’, should be compensated for my time. And any argument that doing so might constitute inducement is ridiculous—I am induced only by my impending mortality. Compensation would merely serve to lessen my financial burden to some degree.

Remember, always remember, that I am a human being. And that when you describe me as either compliant or noncompliant I do not feel respected. 

Know that participation in a clinical trial comes with a certain loss of autonomy. Do not abuse this by favoring the collection of data over my individuality. If a scan or MRI is not clinically indicated, then do not expect me to get one just for the sake of science.

Be aware that not only must I qualify for a trial, I am always at risk of being booted. Whether it is progression itself or a comorbidity that develops once on trial. I had a terrifying scenario several years ago where it appeared I might have developed pancreatitis. When I called my oncologist her first words were ‘I hope it’s not pancreatitis as it would preclude you from participation in any other trials.’ and then she asked me to come in for testing. I refused. Telling her that I may be in a tight situation (I used saltier language) if I had pancreatitis but it was a tight situation with options. If I came in to be tested I would simply be in the tight situation—minus options. This sort of scenario should not exist. 

And lastly, realize that clinical trials are a social contract. Understand and honor my sacrifice in the same way you would a soldier. 

Which brings me to my final ask. 

A year ago I developed resistance to my third ALK inhibitor. In my years of participation in clinical trials I have collected not only side effects and bills, I also have a coterie of resistance mutations. Had it been up to me, I would have pulsed my treatment right from the start, as even to a layman, it made sense that if you take an inhibitor daily, resistance is inevitable. 

However, in this sense I was compliant. And now, eleven years after starting my first phase I clinical trial, I am at the end of the branch. 

There will likely be no 4th generation ALK inhibitor. Certainly not in time for me and perhaps not at all. Why? Because there is no financial incentive. What was 4-6% of those diagnosed with lung cancer has been cleaved and cleaved again by the time you get to resistance with a third gen. 

I am a veteran of these wars. An outlier. And yet, now I must live with the knowledge there is no next treatment.

It is likely that I have now been on this third gen ALK inhibitor longer than anyone else. I am one person. However, as an advocate and activist, I feel the weight of all those who are just behind me. And I ask, what are you going to do when they too develop resistance to a third gen? How will you tell a 35 year old with three kids that there is nothing else to do? 

It is my suggestion that as a part of this social contract, we should not be abandoned. It is a poor return on an investment, it is bad science, and it certainly is not in the best interest of humanity. 

Demand, as I shall be, that our government mandate some sort of umbrella clinical trial to study those of us who are outliers. Honor our contribution. You’ve helped bring us this far, now see just how far we can go. Do not leave us on the battlefield after we have fought so valiantly. Bring us home.

Thank you.