Metastatic Cancer Treatment Since 2010: The Success Stories

post by sarahconstantin · 2024-11-04T22:50:09.386Z · LW · GW · 1 comments

Contents

  Metastatic Cancer Is Usually Deadly
  …So Eradicating Metastatic Cancer is Especially Impressive
  Methodology
  Single-Patient Case Studies
    Stats
    Takeaways
  Larger Studies and Case Series
    Stats
    Takeaways
None
1 comment
Midjourney, “metastatic cancer”

Metastatic Cancer Is Usually Deadly

When my mom was diagnosed with cancer, it was already metastatic; her lymph nodes, said the nurse, “lit up like a Christmas tree.”

Most people with any kind of metastatic cancer — that is, instead of a single tumor, a cancer that has spread to multiple locations in the body — die within the year.

You’ve probably heard of people “surviving” cancer, saved by chemotherapy or surgery or radiation or a new high-tech drug.

If you know more about cancer, you’re aware that “survival” is relative; when there are no observable signs of cancer, you’re considered to be “in remission”, but you’ll always be at elevated risk of the cancer coming back. Still, years-long or even lifelong remissions are possible, and for some cancer types are even now the norm after treatment.

Mostly that’s for cancers caught early, though. Once the cancer is metastatic1, lasting remission is uncommon.

…So Eradicating Metastatic Cancer is Especially Impressive

There are cases where metastatic cancers go into complete remission, however. They’re not common, and it’s an exceptionally high bar for a cancer treatment to clear.

Historically, this was usually only possible in cases where there was a strongly immunogenic cancer (like melanoma) and one of the older forms of immunotherapy was available (like injecting tumor-infiltrating lymphocytes, or a toxic pro-inflammatory signaling agent like IL-2, directly into the tumor to stimulate a strong immune response.)

Now, though, we’re living in a golden age of immunotherapy, and seeing a variety of new approaches to cancer treatment reach the clinic — so it’s worth looking back over the past 15 years to see what treatments have succeeded on the “hardest of hard mode” tests: effectiveness on metastatic (or refractory/relapsed) cancers.

Methodology

I looked through Google Scholar using search terms like “metastatic” and “complete response.”

In cancer clinical trial lingo, a “partial response” refers to some shrinkage of the tumor(s)2, or (in hematological cancers), a decrease in the number of cancer cells.

A “complete response” refers to the total elimination of (detectable) tumors or cancer cells.

Every remission requires a complete response; but it’s possible for a complete response not to last very long before the cancer comes back.

I included studies in which >20% of cancer patients with metastatic solid tumors, or relapsed/recurrent hematological cancers, had complete responses to therapy.

This includes a lot of uncontrolled studies, and some case studies.

Obviously, if a single patient in a case study has a complete response that’s technically “100%”, but that shouldn’t give you the impression that the true complete response rate for that treatment is anywhere near 100%. Case studies are selected for being remarkable. Still, I included n=1 case studies because they’re intriguing and instructive, in a separate section from n>1 case series and studies.

Most studies included here are uncontrolled — they’re retrospective analyses of cases at one or more clinics, or they’re single-arm studies, that tell you the performance of a given treatment but don’t compare it to a “control.”

Because spontaneous regressions of metastatic cancers are almost unknown, virtually any case of a “complete response” from a treatment indicates the treatment works better than no treatment at all, even in the absence of a control group. On the other hand, without a control group it’s much less certain whether some New Treatment + Baseline Treatment is better than Baseline Treatment alone, where the “baseline” standard of care would differ a lot based on the exact cancer type and patient characteristics. Oncologists rarely give any cancer patient literally no treatment unless the patient insists.

Single-Patient Case Studies

Here’s a link to the spreadsheet.

Stats

Takeaways

Larger Studies and Case Series

Here’s a link to the spreadsheet.

Stats

Takeaways

What are the takeaways, for patients, researchers, and the general public?

First of all, this is real progress, not stagnation. I looked for examples of >20% complete responses in metastatic cancers a decade ago, and there’s a lot more out there now than there used to be, mostly due to the results from the new immunotherapies coming in. In some types of advanced cancer, lasting remissions are now a real possibility for nontrivial numbers of people.

Secondly, I think there’s probably a lot more room to improve and expand upon these immunotherapy successes. There are a lot of variables to tweak. Remember that it took a few decades between the first discovery of chemotherapy in the 1940s to the development of effective chemo regimens for solid tumors like breast cancers in the 1970s. Figuring out drug cocktails, dosing strategies, etc, makes a big difference in effectiveness and applicability. Now notice that now, unlike in the mid-20th century, we have the whole molecular biology and immunology toolbox to play with. The range of possible “CAR-T therapies”, for instance, is almost infinite. The optimization process is not done.

I have a good feeling about “old-fashioned” immunotherapy angles — oncolytic viruses, heat-killed bacteria, innate-immune inflammatory toxins like IL-2 and TNF-alpha. This zone was where researchers first started to notice that the immune system might fight cancer; these are simpler, cruder techniques with fewer moving parts than the new hyper-personalized stuff.

And, of course, antibody-drug conjugates are going to hit the clinic in much bigger numbers in the coming years, and we should be pretty hopeful about them; it’s yet another way of putting your cytotoxic drugs where you want ‘em and not where you don’t.

1

Hematological (=blood) cancers are already disseminated throughout the bloodstream rather than lumped up in tumors, so “metastatic” isn’t really a meaningful term there. But an equivalent concept is “refractory” or “relapsed” hematological cancer — a cancer that keeps coming back after multiple rounds of chemo. Like metastatic cancers, refractory/relapsed hematological cancers usually have survival times measured in months.

2

in the often-used RECIST criteria, a partial response requires at least a 30% decrease in the sum of the diameters of all tumors.

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comment by DenizT · 2024-11-21T15:35:01.064Z · LW(p) · GW(p)

Thanks for the great recap, some of this looks very promising! I remember reading your personal blog several years back, you (and James Watson) were both optimistic about the possibility of leveraging the Warburg effect in cancer therapies. Why didn't much progress happen on that front? Is it that we haven't invested the necessary resources there and instead got excited by alternative promising directions? Or did we come to learn of new information that reduced the feasibility of that strategy?

And another thought, it seems like there is some need for rapid experimentation on voluntary patients to optimize protocols (e.g. how many days to fast, whether to do oncolytic virus therapy and immune checkpoint inhibitors together etc.), and the risk-averse hyper-bureacratization around clinical trial protocols seems like a huge impediment to progress for cancer specifically.