Tag Archives: lorlatinib

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.

C’est moi

Freethinker: a person who thinks freely or independently : one who forms opinions on the basis of reason independently of authority especially.

I view the world from two distinct lens. Natural law (an observable law relating to natural phenomena) versus human constructs. And I really, truly only respect the former.

Although I would argue this is a sensible approach to life, I often run afoul of those entities which either hew to or consider themselves The Authority. Undoubtedly this viewpoint started early in my life, when so-called rules got in the way of whatever activity I had planned. My response to being admonished by my parents and or teachers– ‘You are not the boss of me’ was certainly uttered only under my tongue after the first few retorts resulted in a spirited spanking.

Tall, tom-boyed, gap toothed, left-handed, atheist. Non-normative comes naturally to me. Which is not to imply that I am always well received.

What is a breath of fresh air to some is a pain in the ass to others. Just ask my soon to not be landlord.

Or the pharmacist who would not refill my prescription (for a drug I have taken for fourteen years) simply because there was an error in the way it had been transcribed, with it reading both every seven hours and twice a day.

One week later I finally said to him, ‘You know, it doesn’t matter what it says on the bottle, I will take those pills as often as I want to anyway.’ Note added to chart, I would imagine.

Fortunately my oncologist is on board with logic and is a goddess of empathy. As the scrip was for ativan and I was coming off of two sleepless nights per restarting lorlatinib, I was feeling a little desperate. Saturday night I messaged her. She was out (on a date with her husband, I hope) and yet stopped what she was doing to call the pharmacy on my behalf.

That night I slept like a baby. Dreaming dreams unschooled and unkempt. Authority free.

Never really gone

Once you have cancer a headache is not merely a headache, it’s a potential tumor.

My gallbladder issues–although garden variety in nature–were immediately suspect for liver, pancreas, metastases as sources of trouble. Some scary moments there, as each of those scenarios would have meant a further limitation of options. When running on empty, you want to keep the road as clear as possible.

Fortunately my worst fears (like that headache, always in my back pocket) were not realized.

And in true lemonade from lemons fashion, my little adventure resulted in some marvelous insights.

First, that my family is indeed my rock. Good, that.

Secondly, that underneath the me of lorlatinib, my old, true self is extant.

WTF am I talking about? Well, Alice had me hold drug once I’d been admitted. I went six days without therapy. Lorlatinib comes with a host of strange side effects and within days, some of them began to subside. Alice was the first to notice that my speech was not so slow. And suddenly I was intensely aware of everyone’s cologne–I hadn’t even realized my olfactory had been compromised.

My neuropathy in my feet is so severe I can walk around with pebbles in my shoe and not know it. My toenails have all gotten ingrown while on lorlatinib, requiring surgery on eight of the ten. One is still pretty raw but normally I can’t feel it. Suddenly it hurt like hell.

But, best of all, I started to feel like me. My ability to think in an organized and linear fashion had magically returned.

Sigh. It was but a brief visit with myself, as I started back on drug two days ago. Two sleepless nights later I am once again struggling to complete tasks and my toes are numb.

However, there is comfort in knowing that I’ve never really gone.

Hurry hurry hurry up

So. I need a 4th generation ALK inhibitor. Stat. And I’m not encouraged by the fact that it’s been almost five years since lorlatinib, a 3rd generation ALK inhibitor, became available in clinical trials.

And although no one would argue that the 6.8 years of median overall survival that is now a statistical probability for ALK+ patients is a good thing, I can’t help but believe it may have negatively impacted the urgency to identify further ALK inhibitors.

Over here in Linnea Land we are feeling that urgency thing big-time.

Today was scan reviews aaaaaaand……just as I expected the news was not cheery. Continuing progression. Not rapid and yet decidedly of the rampant variety. Upon further questioning, an estimated three to six months until lorlatinib is not going to be enough. Which would be okay if there was in fact anything else.

Symptomatically, I knew as much. A nebulizer is being delivered tomorrow and I will once again become an albuterol junkie. Breathing is some necessary shit and I need to get mine back on track.

Me.

Last weekend I was in Colorado for my niece Mesa’s baby shower. That, and a much needed break from my own reality. Yesterday morning I sat in this egg shaped chair, my sweet spot, and said to my sister Bink: ‘I’m just going to stay. I mean, why would I go?‘ Bink and her husband Greg brought me a smoothie and a latte each morning and a martini every evening. The life, y’all. But my own reality show was calling and I boarded that airplane back to Boston anyway. This morning I was at Yawkey, not eager and yet ready to receive that reality check, gently delivered by Goddess number one, Dr. Alice Shaw.

Sweeeeeet spot. Notice the empty smoothie glass. And that Colorado sunshine.

After an appointment with Goddess number two (my social worker, Mary Susan Convery), I walked to the Boston Common to meet a date because even when, maybe especially when the shit goes down this hard, you need to just keep on living. As loud and as large as life will let you. And sometimes, even larger.

The gorgeous Boston Common.

Personal skinny

I had my every six week oncology appointment yesterday. Echocardiogram, labs, and a consult with Dr. Shaw’s nurse practitioner Jen Logan followed by a visit to my social worker.

It was an opportunity to double back and clarify whether or not the way I perceive my current situation is accurate. And, it would seem, I hold no illusions.

In a nutshell. My cancer is yet ALK+, and therefore partially responsive to inhibition with lorlatinib. However, the two newly acquired secondary mutations are preventing the lorlatinib molecule from binding as completely as before. Hence, the resistance. And–unfortunately–these acquired mutations are not actionable; there is no effective inhibitor for either of them.

Fortunately, my cancer is not aggressive. Nor is it indolent–but after fourteen years, we have a pretty clear understanding of how fast it grows.

Simply put, barring any new developments, I figure two years.

That can feel like a little or a lot, depending on your perspective. And as I have already wrapped my head around a much shorter time frame (3-5 months) I can do this.

However, it is also important to remember that although I am talking about a probability, possibility is not out of the question.

To this end, Jen assured me that Dr. Shaw is reaching out to both chemists and researchers urging them to come up with a magic molecule. It could just happen.

If it doesn’t, we can try a combination therapy. However, unless there is some not yet identified synergistic effect, it is unlikely this approach would be successful for my increasingly resistant cancer.

Worse comes to worse, I could return to chemotherapy (this would be the third time) in an effort to abate symptoms and possibly stabilize the cancer.

As we finished talking about possible scenarios, Jen asked me if there was anything I was particularly scared of or worried about.

I told her that I was sad but not afraid. And still hopeful. As for worries, two things. I’m not crazy about the way I’m going to die. I’d like to remain calm and I understand that not being able to breathe is going to make me feel panicky no matter how much self control I exercise. But my biggest worry is my three kids. They are all grown-ups now (something I am so grateful I got to experience) and I know they’ll be fine but we’d all prefer to have their mom hang around.

It was hard but also good, to speak of the future and the potential lack thereof. Jen asked me how I keep my cool and I told her it was time and practice. This is not my first death rehearsal.

xo

Oh Lorbrena

Like some fancy fantasy girlfriend, the drug formerly known as lorlatinib has been rebranded Lorbrena. And not a cheap date, Lorbrena. Check out these over the counter prices for a months supply:

However, even given her top shelf status, my Lorbrena is handed over in a brown paper bag to be carted home wino style. A brown paper bag that evidently blends into the surroundings so very well, I simply forgot it was there.

Yep. One whole week without taking my cancer meds. Blame it on stress; they sprayed my loft for bedbugs for the third time this week, on the same day I was getting surgery on four ingrown toenails that are an apparent side effect of hanging out with Lobrena all these years. And change; August and Lily moving out did a number on me. Then there’s memory; I just can’t. Remember. And it’s getting worse with time.

So there you have it. Gotta say, I enjoyed my little respite but starting up again resulted in a full on case of the runs and the shakes; just like our first date so very many years ago. And now, in order to keep this relationship on track, I need to begin (duh) setting an alarm to remind me to take my meds. That is, if I can remember to. Maybe I’ll even start filling out the daily diary (I usually do it in the office and when my nurse comes in, I sing a little song ‘making shit up, making shit up.’ Honestly. I am not non compliant for the sake of non compliance but those diaries are busy work. And, this being 2019, you might think we’d have a more sophisticated mechanism for capturing supposed data than a worksheet. I’m over it.

But the taking of the meds? I need to be on it.