Progress in Immunotherapy for MSS

[MadMed]

Some decent results for MSS mCRC, not earth shattering but for people that were on 4th line and basically at the end of traditional treatment this is huge. It would be good to do a trial like the MSI one for early treatment .
An immune based treatment would be so much better than chemo!

Seems that this is useful for non liver mets.

Objective responses:

24% overall response rate
73% disease control rate (partial response + stable disease)
50% objective responses with greater than 50% tumor reduction

Durability:

80% objective responses ongoing at data cut-off
30% objective responses exceeding 1 year

Patient Sub-Populations:

Objective responses in 5 patients with RAS mutations for a 24% overall response rate and 81% disease control rate in this population; other PD-1 combinations in separate trials have reported only rare responses in this population (≤1% response rate)
Responses observed in patients with metastases historically resistant to immunotherapy, including patients with malignant pleural effusions, soft tissue, peritoneal, retroperitoneal, and bone metastases

Tolerability:

Botensilimab was well tolerated, with no grade 4/5 treatment-related adverse events
Rates of gastrointestinal and skin toxicities were comparable to those reported with first-generation CTLA-4 inhibitors

https://www.bakersfield.com/ap/news/agenus-shows-unprecedented-activity-for-botensilimab-balstilimab-combination-in-microsatellite/article_ce636aa6-c0d2-5443-a440-2128c8b5cfe0.html

[Peregrine]

Some decent results for MSS mCRC, not earth shattering but for people that were on 4th line and basically at the end of traditional treatment this is huge. It would be good to do a trial like the MSI one for early treatment . An immune based treatment would be so much better than chemo!
...

Thanks for the info and for the summary!

As you have mentioned, this regimen is mainly for Stage IV patients with recalcitrant tumors, where all previous regimens have failed to inhibit disease progression. It certainly would be nice if they could develop some well-tolerated immunotherapy drugs for Stage II and Stage III patients to replace the standard choices of 5FU, FOLFOX, FOLFIRI, XELOX/CAPEOX, etc. For Stage II and Stage III patients, the list of 1st line chemotherapy options hasn't changed much at all in the past 20 years. Most of the new drugs that have been approved lately have been for treating advanced Stage IV patients, not for delivering neo-adjuvant or adjuvant treatment for non-metastatic cases.

[Nor Cal]

Seems that this is useful for non liver mets.

Could you expand on this? I don't see anything in the link regarding the liver.

[roadrunner]

I think MadMed’s comment (“Seems that this is useful for non liver mets.”) referred to the second bullet under “Patient Sub-Populations,” but in any case I do not think the description or MadMed’s comment were intended to communicate a limitation, e.g., that this doesn’t work on liver mets. I do not see that in the description.

One note: Immunotherapy is really expanding for CRC and this may turn out to be a real beachhead: 24% Overall Response in MSS is amazing if it holds, especially if durable. Disease control, of course, was much higher, *and* responses appeared durable and the drugs were “well-tolerated.” That’s great. It’s a very small study, of course, but a promising result.

Also reinforces the need for all of us to do everything we can to keep immune function optimal.

[Nor Cal]

Thanks for the clarification. Makes sense.

[MadMed]

Thank you RoadRunner, excellent explanation. I wanted to be certain and went and found the actual trial: https://www.cancer.gov/about-cancer/treatment/clinical-trials/search/v?id=NCI-2019-01887&r=1
Indeed, in the exclusion criteria:
19. For participants in the colorectal cancer expansion cohort only: current or previous evidence of liver metastases as determined by computed tomography, magnetic resonance imaging, or biopsy.

I don't understand enough why liver mets are excluded, i'll try to read more. They do insist on good liver function in the inclusion criteria:
2. Adequate liver function, defined as total bilirubin level ≤ 1.5 × institutional upper limit of normal (IULN), aspartate aminotransferase ≤ 2.5 × IULN, and alanine aminotransferase ≤ 2.5 × IULN.

In terms of Peregrine question/comment, from what I am reading, there's a significant split happening between colon cancer and rectal cancer. It is viewed and corroborated that neoadjuvant treatment for CC is similar to adjuvant treatment. For rectal cancer obviously one important goal is organ preservation or avoiding surgery completely. So there seem to be more interest in earlier, pre-surgery evaluation of treatment. And thus, more interest in trying things as a first line as evidenced by the MSI dostarlimab trial as a first line and it's impressive success.

I'm completely with you RoadRunner, i can't imagine that W&W is going to pan out for me, so i see this time before recurrence as buying me time to get to the next thing and getting my immune system in top shape. I seem to be back to normal (albeit on the low end of the range) on my last CBC.

Wish and hope for all of us, but every day, i read something new on CRC, and it's not on mouse models, actual trials!

[Cured]

fellow clubbers, Thanks for the info and the links.

My Onc was funded by Pharma for a phase II study, which went really well. But since I wasn't in it, I cannot get the Immunotherapy (which was shown to be working). The drug company has not yet decided to move on Phase III: so no offer to provide the meds no matter what. I have read so much good about PD-1 inhibitors - and am frustrated that none are available to me (since I'm MSS).

As one of my doctors mentioned that I could not get surgery to remove a spot on my liver due to the fact that I was metastatic and have tumors in my lungs - maybe this is why the studies exclude liver....

I changed back to my original cancer center (away from the NCI center) after this and lack of concern for me as a patient.
Should I be concerned that once we are metastatic that ones treatment options become severely limited? Due to insurance not wanting to pay for someone who will statistically be dead shortly?

Thank God that He comforts me continually. I live on and have hope.

[MadMed]

I’m sorry you’re in this spot cured, but it’s not hopeless!! I’m glad you switched doctors, my view on them is that they’re like car mechanics. Some good ones, some terrible ones and a lot in between.

First, MSS does not exclude you from immunotherapy. If your tumor burden is high enough, you are absolutely a candidate, one of many studies showing usefulness https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8511407/

For liver surgery, i think getting things under control to a point where they can be resected is the first goal. It would not be good to cut half your liver to then have the other half get Mets. You can find surgeons that can cut it, it just has to be coordinated with lungs treatment/resection. You can find some on this board that went through this successfully.

I wish you good luck and some divine help. Push for better treatment and get another opinion. I know MSK does this online, you can get your case reviewed. Get more doctors looking at options for you.

Another link https://jgo.amegroups.com/article/view/21425/html