An oncologist at UCLA told Bess and me that “Head and neck cancer has become a hot R & D area in the last year,” which I find exciting: moving from “a death sentence” to a “a hot R & D area” is great, since I have recurrent and metastatic neck cancer. It started in my neck and has since reached my lungs; if it reaches much further, no clinical trial will be able to help me. I’ve read and quoted research summaries like this one: “Recurrent / metastatic SCCHN [squamous cell carcinoma of the head and neck] have poor prognosis with a median survival of about 12 months despite treatments.” Sounds bad, right? Based on those research summaries, and based on my tumor’s aggression, hitting the median survival range of twelve months seemed unlikely, and in response to those research summaries I wrote essays like “I know what happens to me after I die, but what about those left behind?” But now I’m starting to feel some tentative, fluttering optimism.

Some of that tentative, fluttering optimism is downstream of the Nov. 15 news that petosemtamab / MCLA-158 is shrinking the tumors in my neck and lungs. A UC San Diego (UCSD) Medical Center radiologist estimated that my overall tumor burden shrunk an average of 12.5% between Sept. 5 and Nov. 15. That’s great news. In a phase 1 trial, petosemtamab’s median duration of response was six months, implying that, if I’m the median responder, I have until March – April until the drug stops working and my tumors start growing again. Relative to dying, I’m pleased with the results so far, the median duration of response implies that it’d be a good idea to have a gameplan for what to do next before the crisis. The medical system can move fast at times, but it’s best not to rely on it moving fast: some appointments take weeks or longer between initial contact and the actual appointment.

I’ve been taking the advice that Bess and I give in “Please be dying, but not too quickly: The patient’s perspective: The right hand doesn’t know what the left hand is doing,” in which Bess writes of the challenging, arduous bureaucracy that is the modern medicine clinical trial system:

Establishing Care: Or, this meeting could have been an email […]

To officially be screened for a clinical trial, and matched with one you appear eligible for, you have to “establish care” with a given hospital system. “Establishing care” means, again, making a doctor’s appointment with an oncologist at the hospital. […] Until you’ve had a first conversation with the physician you’re scheduled to see, the physician can’t officially do anything for you, or offer you any advice, even though they can now pull your old medical records. […] If you don’t have a chart and an insurance card? You’re not a person. You say you’re a person without those things? Sorry, not according to hospitals.

Each hospital system differs slightly, too. Some offer telemedicine, while a few won’t. Some will appear not to offer telemedicine but eventually will. Some oncologist appointments can be achieved quickly, while others take weeks. The heterogeneity of the hospitals and systems is itself a challenge. Every hospital system wants to do its own intake, often via phone, during which an intake person asks questions of me (or, realistically, Bess) and then types the answer into a computer that records the answer into a database. The inefficiency of the system is insane, but I also don’t make the rules and I have to conform to the system if I want to not die.

A month ago, I thought the tumors under my jaw and in my neck felt larger. My neck felt stiffer and my range of motion, already restricted, seemed more limited. I had follow-up scans scheduled for Nov. 20, and I expected those scans to yield bad news, so in preparation for the bad news Bess and I made some more establishing-care appointments. Then we found out that the petosemtamab is working, so we didn’t strictly need the appointments, at least immediately, but we’d finagled two telemedicine appointments at UCLA and Cedars Sinai, and another appointment at MD Anderson (“MDA”—which is not to be confused with the euphoric, stimulating entheogen of the same name) in Houston. MDA demanded I show up in person, as if video calls are some weird futuristic technology and not a standard part of everyday life. I’d love to not have to spend time, money, and energy on flying and staying in hotels, but MDA wouldn’t budge. Yet they have a lot of clinical trials, so I bet they tend to get what they want. I don’t want the difference between surviving longer and dying to be a principled stand in favor of telemedicine and against wasting time and money. I’ve also been relatively physically robust lately, so I shut up, bought a ticket, and reserved a hotel room.

The rest of this essay is about that effort to “not die.” It complements Bess’s essay / guide about the clinical trial process and shows how we’ve experienced the later parts of the process. Learning how to effectively navigate clinical trials is an art and skill, which is why Bess’s essay / guide is 16,000 words. Both of us would love for it to be shorter, without the essay / guide losing important detail, but we’re also writing for other people facing the clinical-trial gauntlet, for whom getting this right is a life-and-death matter, as it is for me. If you buy a bike you don’t like or shoes that don’t go with the rest of your wardrobe or food from a fast-casual restaurant that doesn’t satisfy, no big deal. Frustrating, maybe, but ultimately unimportant. Growing lax in finding a clinical trial, though, is like being cavalier about eating wild mushrooms. 

Bess and I also forgot to include a key detail in her clinical-trial essay / guide: in meetings with the oncologists who run the clinical trials, the oncologists will often nudge patients away from trials that don’t appear to be effective, especially if those trials are likely to be closed, and towards trials that are likely to be effective. Each meeting has the potential to uncover non-public information about what treatments are out there. Unpublished knowledge is important.

Our first appointment was at Cedars-Sinai Hospital at Los Angeles, with an oncologist named Dr. Lorber. He thinks my best bet at Cedars is a small molecule called NT219, in conjunction with another, older EGFR monoclonal antibody called cetuximab. Cetuximab isn’t very effective on its own, but maybe it’ll work better in conjunction with another drug. The potential problem with NT219 + cetuximab, though, is that petosemtamab is already an EGFR attack. Once the tumors adapt to it, hitting them with another EGFR attack is unlikely to be successful, because the tumors will have mutated to resist those attacks. Still, in October new data around NT219 was published, showing that, of the four patients who received the highest dose of NT219, two had “confirmed partial responses (PRs).” In the R / M HNSCC world, those are great results. They also demonstrate the usefulness of surviving itself: new data comes out showing that some treatments work, and others don’t. NT219’s mechanism of action is a “dual IRS1/2 and STAT3 inhibitor,” which means nothing to me but is important because it differs from petosemtamab’s mechanism of action.

The second appointment was at MDA.* Earlier I cited Bess’s comment that “this meeting could have been an email;” perhaps the medical version is “This consult should’ve been a Zoom call.” I met live with an oncologist named Dr. Ferrarotto, while I set up my laptop and had Bess in the room via video. MDA has a promising R / M HNSCC trial of a drug called SGN-PDL1V—a name almost, but not quite, as memorable as NT219—from a company called Seagen. SGN-PDL1V is, notably, different in its mechanisms of action from petosemtamab and NT219: “[SGN-PDL1V is a] vedotin antibody–drug conjugate directed to PD-L1 with multiple proposed mechanisms of action including monomethyl auristatin E (MMAE)-directed cytotoxicity, bystander effect, and immunogenic cell death (ICD).” I again don’t know what that means, apart from it differing from the other R / M HNSCC that’ve been recommended to me. I should buy some biochem textbooks and start learning how these drugs really work. Reading textbooks is underrated. MDA has some other promising therapies, too.

Dr. Ferrarotto wanted to confirm that I failed chemo, and I told her the truth: sort of. To back up slightly: most, if not all, clinical trials require that the patient’s cancer show “progression” from the previous treatment(s). In other words, the cancer needs to have gotten bigger (“embiggened” is not the right term, I’ve learned). This rule, however, seems nuts for people, like me, for whom treatments like chemotherapy are only palliative, not curative. Decades of data and experience show that chemo for HNSCC can delay the cancer, but the cancer ultimately overcomes it and kills the patient. Consequently, why wait for chemo to lose its effectiveness? There’s no reason not to seek treatment that might be more effective.

I had a CT scan on July 21 that showed six to eight new tumors, relative to the May 25 surgery (that is bad, particularly after fewer than two months). Then I started chemotherapy on July 24, which Bess and I had planned before we saw the July 21 CT scans; our thinking had been that chemo might kill any microscopic cancer cells still lurking after surgery. Turns out our worry was accurate but we were too slow, and the cancer too fast. Almost as soon as we got the very bad news, we** started seeking clinical trials; if we’d understood more about how common recurrence and metastases are, and how clinical trials work, we’d have begun the process much sooner.

But we didn’t understand how trials work, and no one explained how they work to us, which is why our agitation at our ignorance drove us to write about it, for the sake of others who are as ignorant as we were.

Even though “restaging” scans to evaluate tumor response are usually performed at two month intervals, we finagled scans in early August, hoping those would show enough growth from the July 21 scans that I’d qualify for a clinical trial and not have to exhaust chemo (or have chemo further exhaust me, and exacerbate pre-existing tinnitus, tinnitus being a common side effect of platinum-based chemo). Whoever invented these “you must exhaust the chemo route” rules must not have experienced chemo, because it’s unbelievably arduous. The petosemtamab I’m on now has side effects—tremendous rashes, pain around my finger and toenails, and some others—but it’s still way better than chemo. Besides being more effective than chemo, other therapies might also be less physically horrifying. The August scans maybe, kind of, showed some ambiguous growth that might be sufficient to convince a receptive audience that is on our side.

A tumor board at UC San Francisco Health (UCSF) thought that no, there wasn’t enough tumor growth to justify entering a trial. I guess they also didn’t realize how bad the carboplatin in the chemotherapy was making my preexisting tinnitus. But UCSD thought the growth enough. Great. As of today, I’ve had two chemo rounds and, vitally, when petosemtamab stops working, I can immediately get another round of chemo, and then start the two- to six-week washout period for the next trial drug. The chemo round should be more efficacious than it would’ve been had I gotten more chemo.

To both Bess and me, reserving chemo as a “bridge” between trials seems like it makes more sense than using it up all at once. A lot of the oncologists we’ve talked to will acknowledge this point but nonetheless the whole “exhaust previous line of treatment” rule remains, perhaps due to the FDA. Chemo might be more effective if it’s used sparingly, because the tumors will have evolved to deal with petosemtamab. It’s possible that they’ll be more susceptible to chemo because they’ve faced minimal evolutionary pressure against it. A bunch of oncologists have independently told us that we’re “smart” for this kind of thinking, or they’ve hit us with a neg by saying that we “know how to work the system.” In my view, the system should be set up to maximize both scientific progress and patient wellbeing, which it doesn’t currently do. I don’t want us to have to be “smart” or to “know how to work the system.” I want the system to be smart so that we can be dumb and focus on me getting well, instead of understanding all the nuances we’ve had to master. We’d like to help fix the system.

Anyway, the MDA appointment was helpful and MDA’s top trial is near the top of the list right now. But, I’ll reiterate, the appointment should’ve been a video visit. All else equal it’s better to see people in person, but spending four figures and three days is so wasteful. It’s also a huge barrier to entry. I’d have established care when I was first diagnosed with the recurrence, but the challenges of a trip while suffering the effects of chemo felt insurmountable. If I’d needed in-person evaluation, for surgery to use one example, sure.

The third appointment happened on Dec. 1, about two weeks before my birthday. Bess and I met with a head and neck oncologist named Deborah Wong at UCLA Health, the previously noted doc who told us how head and neck has become a hot research area. Her observation is also congruent with what we’ve noticed in the last few months: there are a lot more promising phase 1 and phase 2 clinical trials than we expected. Data is emerging to show which treatments are working, and a bunch of them are. She thinks a lenvatinib trial is promising, although the same drug was discontinued in a similar HNSCC cohort, so we’re less excited about it now than we initially were. There are a bunch of other trials at UCLA that look good too. If you can afford to live in California, California isn’t the worst place to wind up with head and neck cancer. City of Hope hospital in Duarte also has a bunch of trials.

In the past few months, we’ve learned about a lot of clinical trial study drugs. There’s one called RP3 from a company named Replimune, which is trying to crack the oncolytic virus code. Another is pepinemab. There are others. We’ve also been quietly steered away from some trials, and we appreciate candidness from oncologists regarding trials that aren’t going well.

The overall takeaway is that I’m unlikely to be cured altogether, but my cancer could get turned into a managed diseased for months or, conceivably, years. If I live long enough, I might also become eligible for some re-irradiation. I’d prefer to avoid re-irridation, given how poorly my neck feels right now, as well as how effective, which is to say ineffective, radiation was in Dec. 2022 to Jan. 2023.

There’s a better shot at me living for a few years than I’d thought in July or august. “A better shot” isn’t a guarantee. January scans could show the petosemtamab isn’t working. The next trial I try could fail, leaving the tumors considerably larger and my quality of life concomitantly worse. The same could happen with the trial after that, at which point I’d likely be at or near death. Death is, granted, the endpoint for everyone at current levels of technology, and a meaningful life is important, but I think it easier to face death after a complete life than an incomplete one (it’s been suggested to me by some friends that this isn’t true). Completion is probably not possible for me, but I’m trying to live as meaningfully as possible. Helping others understand how clinical trials work is part of that effort, and part of the effort to accelerate healthcare technology, in however small and limited ways I can. I’ve made some pretty severe mistakes in my economic and intellectual life that inhibit my ability to accelerate healthcare technology and technology more generally, but I’m continuing to try. Trying is better than not trying, in so much of life.

If you’ve gotten this far, consider the Go Fund Me that’s funding ongoing care.

---

* I liked Houston way more than I thought I would, and the parts I saw reminded me of L.A.: lots of differing architectural styles and periods of building right next to each other. A lot of stroads, but stroads that are less wide than Phoenix’s, and thus slightly more humane. Many parking lots, but more tall buildings than Phoenix (though fewer than L.A.). Phoenix is almost all parking lot, and the structures are homogenous and homogeneously boring. If I’d been paying more attention I’d have shot some photos showing what I mean, though I guess most people aren’t as into the way urban structure shapes lives. I just wrote “The quality of your life is the quality of the people you get to know: Illuminating the David Brooks way” and I had a section about the way zoning facilitates loneliness, but I cut it cause the damn thing is already 4k words. 

Houston’s efforts to legalize housing construction also mean that its homelessness problem is much less severe than cities that forbid most housing construction, including Phoenix. The other day Bess and I walked around downtown Phoenix, and after we drove towards home east along Van Buren. The minute one crosses 7th Street, the cityscape shifts from “downtown” back to default Phoenix—parking lot and low-quality retail; if Phoenix liberalized zoning between 7th Street and I-10, or hell 7th Street and 143, there’d be space for many thousands of housing units. Instead of abundance we get tragic scarcity, and low-value retail. But voters keep voting for scarcity, however much scarcity seems ill-advised to me. Apart from Silicon Valley companies, construed broadly, stasis and complacency are the defining features of American life. Bess and I are engaged in a likely futile effort to discourage stasis in healthcare tech, and for more than a decade I’ve been agitating for less stasis in cities. The good news is that we’re seeing some improvement in that domain. In healthcare tech, Jensen Huang (the founder of Nvidia) thinks we’re going to see major progress as healthcare tech moves from science to engineering:

** By “we,” I mostly mean Bess: I was still sick and exhausted from the surgery, and then I got chemo on July 24, which meant I was sick and exhausted from the surgery recovery and from the chemo. Being sick is a full-time job.