In March I learned that the previous clinical trial I’d been on, petosemtamab, had stopped working, and the tumors in my neck were an average of 20% bigger: a lot of growth in an ominously small space. That news set off a furious, exhausting, consuming effort to find the next clinical trial; pick the right one, and I’d get more time with Bess. Pick wrong, and die. The eventual answer was PDL1V, a Seagen-Pfizer antibody-drug conjugate (ADC) that has caused and is causing a lot of side effects—but it’s also working. On April 4 and 5 I got CT scans to qualify for the PDL1V trial, and the CT scans were ugly: the radiologist reported “Progression of disease including tumor interval enlargement and increased extent” and found “enhancement” or “worsening” in every tumor, as well as some lymph nodes. Two large lumps grew from the left side of my neck and jaw. Every day, I felt worse, and headaches began in the last week of March or first week of April. I wasn’t sure whether I’d make it to the next treatment. In mid-March, Bess and I debated whether I should get a round of systemic chemotherapy in order to increase the probability of me living long enough to reach the next treatment. PDL1V, however, requires no more than two previous lines of systemic therapy, and we learned that Seagen-Pfizer would consider an extra round of chemo, even the same chemo that I received in August and September 2023, as a new “line” of therapy—rendering me ineligible for PDL1V.

We decided to hope I’d make it and hold off on systemic chemo. On May 15 I got CT scans after four rounds of PDL1V, and the scans initially baffled Bess and me, because the radiologist reported things like “large irregular areas of enhancing soft tissue… are significantly smaller and not definable on today’s exam.” “Significantly smaller” sounds good, but what does “not definable” mean? The radiologist went on to say: “The largest area seen previously involved the right floor of mouth, right submandibular space and right tongue base. There is soft tissue fullness although no definable mass seen.” “No definable mass” again sounds better than, say, “giant tumor is protruding through the floor of the mouth,” but what gives with the language? Is the radiologist lazy? What are we supposed to do with this? The lung CT scans, meanwhile, are less good, though not completely terrible, with four probable tumors, two of which are the same size as they were in April, and two of which are somewhat larger.

That news is net good, because the neck tumors were so large and in such a confined space that they’re likely to be fatal much sooner than the lung tumors. Still, Bess and I had trouble figuring out what to think about the report, and the report was important because I had to decide whether to persist with PDL1V despite the side effects, or switch to an immunotherapy called BGB-A3055. If PDL1V isn’t working, then the decision is easy. If it’s ambiguously working, then switching probably makes sense. If it’s having a tremendous effect on tumors, then trying to stay on it despite the side effects is probably wise. Plus, there are only two really good clinical trial available right now that Bess and I know about: PDL1V, which I’m on, and BGB-A3055. There’s a third trial of another ADC, Abbvie’s ABBV-400, but that trial also uses an ADC to deliver a gnarly chemo agent called MMAE. If I can’t handle MMAE in PDL1V, I might not be able to handle it in ABBV-400 either. If my tumors don’t respond to MMAE in PDL1V, they might not respond to ABBV-400’s mechanism either. It’s useful to try different mechanisms of action, rather than hitting the tumors with attacks they’ve already not responded to or adapted to.

Running out of good trials will likely be the end for me, though maybe I can get a bit more palliative chemo, and that’s an incentive to try to keep going. Since I wrote about the brutal side effects of the Apr. 22 – May 6 period, I’ve also gotten on drugs to reduce them: dexamethasone (a steroid), aloxi (an anti-nausea drug), Zofran (another anti-nausea drug), Imodium (a stopper-upper that, uh, slows digestion), simethicone (an anti-gas drug), omeprazole (a gastric acid reducer), ativan (anti-nausea for me), bentyl (a drug to treat GI cramping and spasms), and IV hydration (since dehydration contributed to a bunch of the symptoms, and it’s hard for me to drink enough water, despite me feeling like I’m drinking constantly). While the side effects are better controlled, they’re not eliminated. My weight has stabilized and maybe increased by a pound from where it was on May 6, but I’m still hovering in the 133 – 139 lbs range, which is terrible for a guy who is 6’1” and used to weigh 175 lbs. Eating usually hurts my abdomen; pain disincentivizes consumption. I overcome it, at cost.

I’m going through all this to give a sense of the stakes and dilemmas: I can’t be the only person facing these types of problems, and I hope that reviewing my thinking, and Bess’s, will help others who are facing analogous situations, and who are overwhelmed by the number of factors at play. We’ve been exhausted by the amount of attention finding and executing treatment has required, and that’s part of the reason I keep complaining about the paucity of information on clinicaltrials.gov, and how the site should be kept up to date so that others like me don’t struggle as hard as Bess and I have. Unless and until that happens, people who are already struggling with cancer diagnoses (and their families) will have to struggle the way Bess and I have, or die.

Dr. Call, my oncologist at START-Rocky Mountain (where I’m being treated) also said that he can reduce the PDL1V dose to 90% of its current level (which is, I think, 1mg / kg? Or was it 1mg / lbs? I’ll have to look more closely at the label), and a dose reduction may disproportionately reduce side-effect intensity while preserving PDL1V’s anti-cancer properties. That’s attractive. Yet I hesitate, because I wonder: could I be on the verge of eliminating some tumors from my neck?

“Eliminating some tumors” is improbable but not wholly impossible. On Friday, Bess actually talked to Dr. Diegnan, the radiologist at SMIL who read my neck CT and left those seemingly inscrutable comments about the tumors being “not definable.” She saw a “very good” response in the neck, to the point that tumor can’t be distinguished from asymmetric fibrosis that blends into the neck muscles. Distortions from extensive surgery and radiation make it too hard to say whether tumor ends and other tissue begins—the tissues all look like each other. She also said that she, too, hates vagueness and a lack of measurements, but there wasn’t really anything she could measure: “It [the tumor definition] was clear in April. His disease was so bad.”

It’s possible that the tissue asymmetry is from tumor, or that it’s post-operative and post-radiation change, but the improvement over six weeks is clear. Some of the tumors may even have disappeared, and, while she’s not allowed to speculate in the official radiology report about whether the lack of tumor definition means a lack of tumor, she had some hopeful theories. She also recalled seeing my original MRI in 2022, since my diagnosis and relatively young age stood out. In looking at my previous scans, she volunteered that “I haven’t seen [tumors / a cancer] this aggressive or this fast.” This is from a radiologist who sees a fair amount of cancer. The cancer pros note, independently of one another and without prompting, that mine is spectacularly, uncommonly bad.

Bess and I found ourselves thinking about the two rounds of spot radiation I’d gotten, on Apr. 24 and 26. I knew already that chemotherapy can potentiate radiation therapy. I idly searched for “MMAE” and “radiosensitizes” and found that MMAE appears to be exceptional: “we report therapeutic synergies of targeted cytotoxic auristatin radiosensitization to stimulate anti-tumor immune responses.” Another paper finds that “MMAE sensitized colorectal and pancreatic cancer cells to [ionizing radiation].” Those two papers aren’t the final word, but it’s possible that radiation therapy was unexpectedly efficacious because it acted synergistically with MMAE. That could help explain the incredible response in the neck tumors and indifferent response in the lungs. I quit the spot radiation because of how terribly I was doing the week of Apr. 22, but maybe that was an error. I don’t want to cling to false optimism, but what if there’s an opportunity in PDL1V for incredible, unexpected response?

The net result is that I’m more likely to see 2025 than I’d have thought a month ago, though that likely requires PDL1V to continue working in me, and for BGB-A3055 to work after it. Neither is impossible. The possible resolution of some neck tumors is incredible and buys me more time. I wish there was less suffering and fatigue; Dr. Call says my response to PDL1V is unusually bad. Losing six to ten pounds between Apr. 15 and May 1 spooked me. Back in September, I got on petosemtamab, and by December I’d eased into a pattern of twice-monthly infusions, with side effects that were unpleasant but  bearable and predictable. For the last two months, I’ve felt whiplash, as I get spun from surprise to surprise to surprise. I’d love to find a consistent pattern that allows me to turn my attention elsewhere, though a big part of the reason I’m still alive is meticulous, continuous attention to these problems, and the management of treatment possibilities.

I find myself wondering, too: how many of the lung tumors are truly tumors? Could some be “ground glass opacities,” or something else? While I don’t want to get high on my own supply of hopium, the behavior of the lung tumors is surprising and confusing, and I also don’t want to exclude low-probability, real-possibility hypotheses.

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