Category Archives: ALK mutations

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.

Profanity and profundity

At the age of ten I possessed a diary; red, covered in naugahyde, and secured by a lock and key. Its primary function was as a repository for each notable expansion of my vocabulary. Wonderful words like twat, that curled my tongue and piqued my imagination.

My classmates were one reliable resource, but I also scoured books that I pulled from my parent’s shelves. A quick study, I became incredibly adept at skimming until I got to the juicy parts.

Although I understood the need to be discreet per my prurient interest, it never occurred to me to be ashamed. I was curious, and frankly fascinated by not only what was being described, but the words themselves. There are so very many forms of human expression.

I also grew up in a strict and fairly repressive household, those books on the shelves notwithstanding. It would take a good long time before I became comfortable enough to simply be myself. Rather a bit of a randy (turning an adjective into a noun for my own purposes).

Or, as I was described (to my delight) by some young women: ‘dirty but elegant.’ A sentiment recently echoed by my friend Kate B: ‘so regal but can still tell a person to fuck off.’

My self description would be dignified but profane.

Megan Rapinoe just publicly apologized for using the word fucking. ‘“I stand by the comments that I made about not wanting to go to the White House, with exception of the expletive,” she said. “My mom would be very upset about that.’

Now I hear her. My mother would be upset if she heard me speak. However (and I am not representing a franchise like Megan is and my mother is deceased), I do not feel the apology was warranted.

I just made a presentation to GE where I used the word fucked three times. It is possible that some in the audience felt offended, but fucked belongs in my narrative. It describes actual words I used (communicating to my oncologist) and at the time seemed like the most expedient, honest and (yes) elegant way to describe how I was feeling.

What we refer to as ‘swear’ words are valid and time proven forms of verbal expression. And, to be honest, I don’t really understand how people can find them offensive.

Cancer offends me. And if a dirty word helps me get that point across, well then I will damn well utilize it.

xo

The ugly

Ouchy.

After fourteen years and three clincal trials, my veins are as heavily trafficked as a junkie’s. And getting a needle in there is not for the faint of heart.

The first nurse who tried to take my blood in the ER simply gave up. No shit. “A new shift is coming on” she said. Several hours later nurse number two gave it a go and the aftermath is above.

Clearly all phlebotomists are not created equally. Thank the heavens I am not needle phobic or I might have given up the ghost long ago.

I share this little bit of ugliness simply to remind all that cancer is a multi-faceted disease. There is the injury but also the insult. The simple but not so simple little shit that we all put up with on a daily basis.

The collateral damage that comes from living with a chronic disease that requires both constant treatment and attendant monitoring. I mean, I can’t even fathom the amount of blood that has now been drawn from my body. Liters upon liters. Years upon years.

Just part of the price I pay to hang with y’all a little bit longer.

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.

Throwing shade

Just go away, you sticky little bastards.

I talk to my cancer, and that was this morning’s heartfelt greeting.

Yes. After years of hardcore warfare, my body the battle ground, I’m trying another approach.

Not a surrender, not a truce, but rather one in which I attempt to understand where the enemy (that would be cancer) is coming from. Not go high, go low.

It’s such a bizarre concept, my own cells run amuck. Unlike a virus, which can jump hosts, when I die, my cancer dies. Lose lose. Total annihilation.

Of course, it’s wrong to assume that this is not an end unto itself; The End. I mean, we all know this planet’s getting crowded. Of course, in this particular case, it sucks to be part of the solution.

I also think that part of the genius of DNA is the possibility for error. A consistent state of stasis is one big drag. Given the rate at which DNA replicates, errors of transcription offer fresh possibilities. Mutations allow life to evolve but they certainly can wreak havoc on an individual organism.

Which brings me back to my morning conversation. At this point I am at some sort of personal ground zero. Not emotionally (I am fine, really fine) but rather at a loss per how to address these errant cells of mine.

As captain of this ship, I can’t help but feel that a mutiny is under way. “If my body goes under, you go with it.” I tell these rogue cells. “Your ways are self serving and short sided. By gobbling up everything, you shall kill us all.”

Of course I see the parallels—what we humans are doing to the earth is not so very different than what my cancer is doing to me.

“What’s the point?” I say. “Why can’t we all live in harmony?”

These little bedside chats are my attempt to stay reasonable. But cancer is beyond reason. If I am to survive, I’m gonna have to fight–probably dirty.

Hey cancer, nobody likes you.

Cancer, well, cancer don’t care. And that’s the flipping problem.

Yes to this

Imagine a health care system based on these principles:

Services are funded through progressive taxation, so access is based on need, not ability to pay, and financial contributions are based on wealth, not health.

That’s the German model, as reported in the NYT’s today.

Although I have felt blessed to reside in a country where I’ve had access to cutting edge medical research, it has also meant that I max out my deductibles in the first two months of every calendar year. The end result is that more than one third of my income has gone to healthcare. Incredibly stressful and not a tenable situation. In short, there has to be a better way.

For a more in depth look at the German model, follow this link: The German Healthcare System