Tag Archives: SHP2 and lorlatinib

Where have all the rabbits gone

There were some major highlights to today. A quick meet-up with Patty Watkins (and a photo-op with the white ribbon she brought me). Hugs from not one but both of my oncologists. Lunch with one of them (Alice) and coffee afterward with Brad Power, who is hosting the Linnea Olson hackathon. Brad and I had not met outside of zoom, and we were each surprised by how tall the other was (we’re all small online).

Less festive was the stark reality of where I’m at. In short, it’s getting increasingly less likely that any rabbits will be pulled out of hats.

On a plus side, that biospy is an enthusiastic go, as there is plenty of tumor to harvest now. By the end of next week or, at the latest, early the following week, I shall be back on the table.

I also signed a new protocol today, for the lorlatinib/TNO155 trial. TNO155 is a SHP2 inhibitor and paired with lorlatinib there may be a synergistic/anti tumor effect. It is very early in a phase I trial (I shall be the second participant at MGH). And, occular toxicity is a potential side effect. Given the blisters on my retinas while on binimetinib and lorlatinib, I could have been precluded but permission was given as long an eye exam pre-trial shows no abnormalities. And, of course, I shall be followed closely by a retinal specialist once enrolled.

So. There is that. An option. Today was a day for straight talk so I asked the what ifs. If I progress or experience side effects that would disqualify me from the trial, what else is there? Dr. Lin said we would peruse a portfolio of phase one trials at that point (clearing house). And, there are two potential fourth generation ALK inhibitors in the pipeline, but I may not fit the requirements for the first one or the timeline for the second (early 2022).

And then I moved the conversation to worst/best case scenario. If I don’t respond, six, seven months? She was slightly more optimistic, feeling I could make it through the holidays. And best case? Well, I’m not likely to reach seventy. Maybe not even sixty-five–and this is based on the irreversible damage in my lungs. However, if I have an opportunity to try and respond to multiple treatments, she felt a few more years were reasonable.

Just yesterday I was thinking about what it was like to simply assume that you would live another twenty years. And also about how long it had been since I had assumed/presumed anything of that sort.

That said, I have always felt that I had the potential to reverse what was happening to my body. Against the odds, but possible.

I no longer believe that to be true. This is based on my recent scans, but also how I am feeling. Exhausted. Often short of breath. And for the first time, in pain. Alice said this is either pleural effusion or tumor pressing on the adjacent nerves. Yesterday I had a five hour zoom meeting and I was out of tylenol. This girl poured some bourbon in her coffee cup. I shared this with Jess today and her only comment was at to whether or not it helped. And it did.

So, that’s the naked skinny. In all its unclothed veracity.

The ugly reality. That’s my most recent scan on the left—ten weeks ago on the right. My left lobe is disappearing.

Like a whisper

“I came to live out loud.” Emile Zola.

And so I did. But over the past week or so I have been living quietly. Grieving, as yet another friend passed. A person too bright, too young, too loved. And yet, too soon gone.

Healing. I have a lot of healing to do. Physically and emotionally. A respite, if you will, before the next trial.

My latest scans were essentially stable. Not according to the radiologist, who saw progression. My oncologists always review the scans themselves, and Jess felt they were unchanged. I’ll go with her assessment.

As far as next course of action, I will likely enroll in the Lorlatinib/SHP2 inhibitor trial.

My big concern is that like binmetinib, a MEK inhibitor, SHP2 inhibition has the potential for retinal side effects. So that is an if for me.

However, by the time I would start, there should be several others enrolled and therefore additional data per potential adverse events.

In two weeks, I will check in with my team. In a month, scan again. And then, maybe, rock and roll.

In the meantime, this space traveler is enjoying the hell out of not feeling like shit.

And the goddess concurs

Alice called me today and we went over my scan report as well as my visit with Jessica Lin yesterday.

She is on board with a repeat scan in five weeks and then, almost certainly, a switch in treatment. Binimetinib plus lorlatinib is finishing up phase I so I would be entering at either phase IB or II. Most importantly, it will not preclude me from entrance into the SHP2 plus lorlatinib trial when that begins enrolling.

Her final assessment is that DS-1062a likely slowed down the pace of my cancer. However, given both the difficult side effects and the modest response, she agreed that it makes sense to give something else a go.

Not gonna lie, it’s always a bit scary moving from one treatment to another. And even though I am more than ready, progression is never a good thing.

Today I am totally wiped out but have also been wrapping my head around what is next. Back into the unknown. However, from this moment forward, I am focusing on recovering from yesterday’s infusion. Which is a postive.

Kumo is with his goddess, Susan. She spoiled him with long walks and a roasted turkey breast for dinner. I have been in my pajamas all day long–a rare but much appreciated luxury. My friend Diane came by briefly after her own scans the day before yesterday, and she dropped off a salmon filet which I finished this evening.

Thank the universe for good friends, stellar oncologists, and options.

xo

Game plan

My sense of where I am at and my scans are in agreement. And although I can continue to entertain the notion of free choice, Dr. Lin said today we were coming to that place where a switch in treatment is likely indicated.

First, the radiology report:

FINDINGS:

Lungs and Airways: There has been a prior LEFT lower lobectomy. Again noted are multiple peripheral nodules in the LEFT upper lobe the largest of which measures 1.5 x 1.3 cm on image 157 series, 4 unchanged from 9/15/2020, but increased from 8/3/2020 when it measured 1 cm. Other LEFT upper lobe nodules are stable in size and number. There is some persistent patchy enhancing 3 x 5.1 cm masslike opacification in the LEFT upper lobe image 245 series 4 that is also stable compared to the prior exam but slightly larger compared to 8/3/2020 when it measured 1.7 x 4.8 cm. While this may represent increased atelectasis, progression in consolidative tumor also possible.

There are multiple stable peripheral nodules in the RIGHT upper lobe and along the minor fissure. The nodule along the minor fissure measures 8 mm image 160 series 4. No right-sided new nodules are noted. No new nodules are noted. Airways are patent.

Pleura: There is a persistent loculated pleural effusion with increased loculation superiorly and posteriorly.

Of greatest concern is the (currently stable) spread to my right lung, the increased loculation of the pleural effusion, either greater consolidation of my largest (3 x 5.1 cm) mass or increased atelectasis, and the fact that one of the nodules in my upper left lobe has increased in size to 1.5 x1.3 cm from 1 cm when I was scanned on 8/3/20. Not rapid growth but also not slow.

The plan is to infuse DS-1062a one more time today. Scan in five weeks and revisit a decision then. The assumption is that I would start on a trial of binimetinib (a MEK inhibitor) and lorlatinib (ClinicalTrials.gov NCT04292119), but once the SHP2 plus lorlatinib trial becomes available, make a switch. Tell you what, I’m going to get a belt dedicated to trial participation, and start making notches on it.

So there you have it. No angst about throwing away a realistic option as my continuing progression concurs with my personal assessment. I asked about the side effect profiles of both binimetinib and SHP2 and am encouraged. First, they are oral medications (no more chemo!) and, as petty and paltry as this might sound, there is no hair loss. Goodbye buzz cut, hello curls, eyebrows, and eyelashes. Adios mouth sores. Hello my old friends diarrhea and constipation (manageable).

Of course, a new trial means more biopsies and initially more frequent visits. I’m down with that too.

Looking forward to a fresh start. I’ve got places to go and people to do! Kidding. I mean yes, once upon a time. But pandemic et al, you do you and I’ll do me 😉

But once I start feeling better (a forgone conclusion) and I’ve got my blond locks back, I’ll be back in the game.

xo