The Colon Club

All,

This is a very early study with only 24 MSS CRC patients but the results are very encouraging. The more I look into it the more promising the results are and I felt the need to share this news.

In a nutshell the combination of Stivarga/regorafenib + Nivolumab had an Objective Response rate (tumor shrinkage of 30% and no new lesions) in 33% of MSS CRC patients (n=24). But that’s not all. If you look at the waterfall for CRC, 87% (21/24) of MSS CRC patients had stable disease, with only (5/24) having any significant lesion growth. Furthermore if you look at the waterfall for all patients, the best responders were on the lowest dose (80mg) and this is what’s recommended for further study. The standard dose for regorafenib (monotherapy) was 160mg, recently the Redos study showed starting at 80mg and escalating weekly to 160mg unless toxicity is reached is superior to the standard dose. This immunotherapy combination recommends using the lowest possible dose of regorafenib (and hence fewer side effects).

The biggest downside of this study is the short follow up (less than a year) duration so we don’t yet know if the responses are as durable in as say Pembrolizumab for MSI patients. But if you look at the spider plot for tumor response, it looks that at least for partial response patients the response may be somewhat durable. We’ll know more once the data matures, and I’m sure there will be many more studies looking into this. I think it’s fair to say this is by far the best response to immunotherapy in MSS we’ve seen.

Here is the best part. Regorafenib is already approved for advanced mCRC. Nivolumab or Keytruda are already on the market so any doctor can prescribe them right now, off label. (Nivolumab and Pembrolizumab are both Pd-1 inhibitors so they should be interchangeable). The main problem will be insurance reimbursement for the off-label immunotherapy. I’ve already heard of oncologists trying this with patients based on this study’s data. If I could handle Regorafenib and I had no other options, I would try this right now. If I have a therapy that’s working, I’d likely try to wait 6-12 months for more mature data, or tough it out until progression.





Regorafenib dose optimization study (ReDOS): Randomized phase II trial to evaluate dosing strategies for regorafenib in refractory metastatic colorectal cancer (mCRC)
https://ascopubs.org/doi/abs/10.1200/JCO.2018.36.4_suppl.611

Thanks Pyro70, it does sound encouraging!

This is great, Pyro! Please keep us updated on any new developments! This is exactly the kind of thing that could turn into a game changer for so many of us!
Cynthia

Thanks for posting this Pyro70! Any promising research avenue is wonderful to read about.

Claudine

Made an accidental pocket post. Can’t figure out how to delete so. So I edited it. Sorry

Pyro70 wrote:All,

This is a very early study with only 24 MSS CRC patients but the results are very encouraging. The more I look into it the more promising the results are and I felt the need to share this news.

In a nutshell the combination of Stivarga/regorafenib + Nivolumab had an Objective Response rate (tumor shrinkage of 30% and no new lesions) in 33% of MSS CRC patients (n=24). But that’s not all. If you look at the waterfall for CRC, 87% (21/24) of MSS CRC patients had stable disease, with only (5/24) having any significant lesion growth. Furthermore if you look at the waterfall for all patients, the best responders were on the lowest dose (80mg) and this is what’s recommended for further study. The standard dose for regorafenib (monotherapy) was 160mg, recently the Redos study showed starting at 80mg and escalating weekly to 160mg unless toxicity is reached is superior to the standard dose. This immunotherapy combination recommends using the lowest possible dose of regorafenib (and hence fewer side effects).

The biggest downside of this study is the short follow up (less than a year) duration so we don’t yet know if the responses are as durable in as say Pembrolizumab for MSI patients. But if you look at the spider plot for tumor response, it looks that at least for partial response patients the response may be somewhat durable. We’ll know more once the data matures, and I’m sure there will be many more studies looking into this. I think it’s fair to say this is by far the best response to immunotherapy in MSS we’ve seen.

Here is the best part. Regorafenib is already approved for advanced mCRC. Nivolumab or Keytruda are already on the market so any doctor can prescribe them right now, off label. (Nivolumab and Pembrolizumab are both Pd-1 inhibitors so they should be interchangeable). The main problem will be insurance reimbursement for the off-label immunotherapy. I’ve already heard of oncologists trying this with patients based on this study’s data. If I could handle Regorafenib and I had no other options, I would try this right now. If I have a therapy that’s working, I’d likely try to wait 6-12 months for more mature data, or tough it out until progression.





Regorafenib dose optimization study (ReDOS): Randomized phase II trial to evaluate dosing strategies for regorafenib in refractory metastatic colorectal cancer (mCRC)
https://ascopubs.org/doi/abs/10.1200/JCO.2018.36.4_suppl.611

Hi Pyro70,
Can I have a copy of this article? I spoke to my oncologist about this and he think I would benefit from this treatment. Can I PM you about this?
Thanks.

tbt4snow wrote:

Pyro70 wrote:All,

This is a very early study with only 24 MSS CRC patients but the results are very encouraging. The more I look into it the more promising the results are and I felt the need to share this news.

In a nutshell the combination of Stivarga/regorafenib + Nivolumab had an Objective Response rate (tumor shrinkage of 30% and no new lesions) in 33% of MSS CRC patients (n=24). But that’s not all. If you look at the waterfall for CRC, 87% (21/24) of MSS CRC patients had stable disease, with only (5/24) having any significant lesion growth. Furthermore if you look at the waterfall for all patients, the best responders were on the lowest dose (80mg) and this is what’s recommended for further study. The standard dose for regorafenib (monotherapy) was 160mg, recently the Redos study showed starting at 80mg and escalating weekly to 160mg unless toxicity is reached is superior to the standard dose. This immunotherapy combination recommends using the lowest possible dose of regorafenib (and hence fewer side effects).

The biggest downside of this study is the short follow up (less than a year) duration so we don’t yet know if the responses are as durable in as say Pembrolizumab for MSI patients. But if you look at the spider plot for tumor response, it looks that at least for partial response patients the response may be somewhat durable. We’ll know more once the data matures, and I’m sure there will be many more studies looking into this. I think it’s fair to say this is by far the best response to immunotherapy in MSS we’ve seen.

Here is the best part. Regorafenib is already approved for advanced mCRC. Nivolumab or Keytruda are already on the market so any doctor can prescribe them right now, off label. (Nivolumab and Pembrolizumab are both Pd-1 inhibitors so they should be interchangeable). The main problem will be insurance reimbursement for the off-label immunotherapy. I’ve already heard of oncologists trying this with patients based on this study’s data. If I could handle Regorafenib and I had no other options, I would try this right now. If I have a therapy that’s working, I’d likely try to wait 6-12 months for more mature data, or tough it out until progression.





Regorafenib dose optimization study (ReDOS): Randomized phase II trial to evaluate dosing strategies for regorafenib in refractory metastatic colorectal cancer (mCRC)
https://ascopubs.org/doi/abs/10.1200/JCO.2018.36.4_suppl.611

Hi Pyro70,
Can I have a copy of this article? I spoke to my oncologist about this and he think I would benefit from this treatment. Can I PM you about this?
Thanks.

Of course feel free to PM me. Unfortunately, I don’t have more material than the posters I shared and the abstract link below. The abstract mentions an updated bio marker analysis, I’d love to see it, but haven’t seen anyone post about it.

I’m excited to see some oncologists pursue this off-label and have heard others doing so as well.

I can’t tell from your Signature. Are you Microsatellite Stable or Do you have Microsatellite instability? Either way, with your TMB immunotherapy is worth a shot.

https://meetinglibrary.asco.org/record/172421/abstract

Thanks Pyro70, I’m MSS. I’m hoping dr will work on insurance coverage soon for nivolumab. My current treatment with folfox and oxaliplatin give me really bad neuropathies right after the 1st treatment so this can’t go far.

tbt4snow wrote:Thanks Pyro70, I’m MSS. I’m hoping dr will work on insurance coverage soon for nivolumab. My current treatment with folfox and oxaliplatin give me really bad neuropathies right after the 1st treatment so this can’t go far.

Do you mind me asking, did you suggest this regiment or was it your oncologist’s idea?

I think it’s hard to do more than 12 rounds of oxaliplatin without risking permanent neuropathy. The problem with oxi is that the neuropathy can get worse after stopping treatment, so you don’t even know how bad it is while receiving treatment.

I informed my onc of the neuropathies problem and he said this can’t go on for long so we have to look at other options. So I showed him your post. He reviewed and agreed we should pursue this option. Thank you so much. This gives me hope.

tbt4snow wrote:I informed my onc of the neuropathies problem and he said this can’t go on for long so we have to look at other options. So I showed him your post. He reviewed and agreed we should pursue this option. Thank you so much. This gives me hope.

Amazing. Please keep us posted on how it’s going. I wish you the best!

tbt4snow wrote:I informed my onc of the neuropathies problem and he said this can’t go on for long so we have to look at other options. So I showed him your post. He reviewed and agreed we should pursue this option. Thank you so much. This gives me hope.

That’s pretty impressive guys - well done! Best of luck tbt4snow

I’m linking a video that has a good discussion on this combo. One thing the presenter makes clear is that these results were really unexpected and promising, but will need to be validated (including in non-Japanese patients). He also speaks to the impressive results of the combo versus mono therapy for each drug individually (responses are less 5% for both drugs given as mono therapy).

https://youtu.be/OD9G2GnbUxk

The relevant discussion starts at 42:30.

Thank you for starting this thread, Pyro70. Today, our oncologist recommended the Regorafenib (Stivarga) + Nivolumab (Opdivo) regimen for my dad. Our onc cited this study and informed us that he has several other patients who will start this regimen under his care.

My dad will start this regimen in about two weeks as that’s how long it might take for the paperwork to go through. Maker of Opdivo will provide it at no charge after receiving proof of insurance rejection. Since Opdivo is currently not approved for MSS patients, we expect his insurance to reject the claim.

Background info:

My dad has been on Avastin for the past three years to keep his lung mets in check. The mets have grown in recent months, so my dad went on FOLFIRI + Avastin. CT scan after four rounds showed stable disease. My dad has been absolutely miserable on FOLFIRI + Avastin and really wanted to try something else. Since being diagnosed in 2013, he has had 89 rounds of chemo and is physically and mentally exhausted.

I will post updates after he starts treatment. Best luck to everyone on this journey.

ForDad wrote:Thank you for starting this thread, Pyro70. Today, our oncologist recommended the Regorafenib (Stivarga) + Nivolumab (Opdivo) regimen for my dad. Our onc cited this study and informed us that he has several other patients who will start this regimen under his care.

My dad will start this regimen in about two weeks as that’s how long it might take for the paperwork to go through. Maker of Opdivo will provide it at no charge after receiving proof of insurance rejection. Since Opdivo is currently not approved for MSS patients, we expect his insurance to reject the claim.

Background info:

My dad has been on Avastin for the past three years to keep his lung mets in check. The mets have grown in recent months, so my dad went on FOLFIRI + Avastin. CT scan after four rounds showed stable disease. My dad has been absolutely miserable on FOLFIRI + Avastin and really wanted to try something else. Since being diagnosed in 2013, he has had 89 rounds of chemo and is physically and mentally exhausted.

I will post updates after he starts treatment. Best luck to everyone on this journey.

Thank you for sharing this info. It’s good to know some of the manufacturer is willing to provide the drug for free. I know we would all appreciate you sharing your experience with this combo. I’m hoping for you, and all of us, that the Japanese results are real and you’ll see a durable response with limited side effects.

FYI, I’m reposting from the MSS Facebook group. There are also two trials one can join to test this combo. Pembrolizumab should be equivalent to nivolumab and there is a trial in Southern California and Florida. There is also a trial recruiting in Florida for reg + Opdivo.

NCT03712943 (rego + nivolumab (Brand name Opdivo; anti PD-1))

NCT03657641 (rego + pembrolizumab (Brand name Keytruda (anti PD-1))

Interesting there is also this trial below that is completed, that I would love to see the results for:
NCT03081494 (rego + spartalizumab/PDR001 (experimental anti PD-1 by Novartis))