The Colon Club

Update of my mom's situation. 3-4 litres of ascites is just confirmed present so Irinotecan and Erbitux officially failed.

Next steps: paracentesis and Keytruda. Our onc ruled out Stivarga and Lonsurf so I guess Keytruda is our last resort.

Exhausting chemo regimens in less than a year. To say we are worried and disappointed is a huge understatement. I try to stay positive knowing quite a few forum members have success on Keytruda.

Never thought this dreaded disease could be this aggressive.

I am sorry, I hope the next treatment works. Keep trying to stay positive, the fight isn't over yet.

Thank you. Now I am waiting for the MS status confirmation. I am really worried though because MSI-H seems very unlikely, and there is currently no MSS trial available where I live.

MSI-H or not, our onc was really recommending Keytruda...

LMighty wrote:MSI-H or not, our onc was really recommending Keytruda...

That is nice to hear from the doc : )

I tried to reply to your question in this other thread:
viewtopic.php?f=1&t=57995&p=456927#p456927

Maia wrote:

LMighty wrote:MSI-H or not, our onc was really recommending Keytruda...

That is nice to hear from the doc : )

I tried to reply to your question in this other thread:
viewtopic.php?f=1&t=57995&p=456927#p456927

Thank you so much Maia. That is really helpful.

What our onc said was that Keytruda works "best" for those with MSI-H and there were "some" successful case even for non-MSI-H. At that moment I thought the message was "it's the last resort so let's just try it regardless of stats". Not sure if he would be willing to try or ever considered the combined use of Keytruda + something. Definitely something I will ask him tomorrow.

Thank you, again.

I'd say trying Keytruda on its own, first, it's a very sensible approach. It might work just well, on its own --I personally know at least one person in that situation, MSS-- and surely will give your mom a break from chemo! I was just mentioning the other options so you know that even Keytruda wouldn't be the last option : )
The most important thing will be your mom quality of life. Hope she improves greatly in this treatment!!!

Talked to the onc just now. He said ascites implies a more life-threatening outlook, so to control the symptoms ASAP, Keytruda is worth trying, considering it's potential and minor side effects, regardless of the patient's MS status.

He is very willing to use Keytruda along with other drugs if the initial rounds with Keytruda alone do not produce favourable results. Apparently I was not aware that the use of drugs in my country (Hong Kong) is much more liberal...

So as Maia said, Keytruda would not be the last option. I just hope there is enough time left for Keytruda to work its magic.

Thanks again Maia. You have pointed us to the right direction and given us hope.

LMighty wrote:Talked to the onc just now. He said ascites implies a more life-threatening outlook, so to control the symptoms ASAP, Keytruda is worth trying, considering it's potential and minor side effects, regardless of the patient's MS status.

He is very willing to use Keytruda along with other drugs if the initial rounds with Keytruda alone do not produce favourable results. Apparently I was not aware that the use of drugs in my country (Hong Kong) is much more liberal...

So as Maia said, Keytruda would not be the last option. I just hope there is enough time left for Keytruda to work its magic.

Thanks again Maia. You have pointed us to the right direction and given us hope.

I agree. No harm in trying Keytruda at this point regardless of MS status. Hoping for the best for you guys.

Thank you plastikos!

Update: The MS status test result won't be available until after a week at earliest. After discussing with the onc we decided to go for the first round of Keytruda on Monday anyway. We don't want to wait in fear of significant progression anymore.

Meanwhile we are considering trying this regimeni in the future if my mom's MS status turns out to be MSS:
http://oncologypro.esmo.org/Meeting-Res ... ancer-mCRC
Our onc agrees to evaluate the possibility beforehand. Unfortunately Tecentriq is not officially approved in Hong Kong so our onc needs to specifically order it from the manufacturer and it could take weeks for the drug to be delivered, and it could be more expensive.

LMighty wrote:Update: The MS status test result won't be available until after a week at earliest. After discussing with the onc we decided to go for the first round of Keytruda on Monday anyway. We don't want to wait in fear of significant progression anymore.

That is so proactive from your mom's doc, how great.

Meanwhile we are considering trying this regimeni in the future if my mom's MS status turns out to be MSS:
http://oncologypro.esmo.org/Meeting-Res ... ancer-mCRC

Of course. That regimen has been discussed extensively in different threads in this forum. We have a fellow, ACPdiddy, in that trial viewtopic.php?f=1&t=57849&p=455797
There are other similar trials ongoing. One that adds bevacizumab --Avastin-- to cobimetinib and anti PD-L1, NCT02876224; that is interesting because adds an agent that we know it is active on mCRC. Other trial for MSS NCT02060188 combines cobimetinib + anti PD-1 + anti CTLA4 --Yervoy, an already approved immuno for melanoma.

LMighty: atezolizumab/ Tecentriq is an anti PD-L1. Even if it has a slightly different mechanism of action than an anti PD-1 --as pembrolizumab/Keytruda or nivolumab/Opdivo are--, so far everything points to the fact that they have similar results.
So, the combination of Keytruda with cobimetinib --Cotellic-- or any other MEK inhibitor available in Hong Kong --like trametinib (Mekinist) should be equivalent.

Maia wrote:

LMighty wrote:Update: The MS status test result won't be available until after a week at earliest. After discussing with the onc we decided to go for the first round of Keytruda on Monday anyway. We don't want to wait in fear of significant progression anymore.

That is so proactive from your mom's doc, how great.

Meanwhile we are considering trying this regimeni in the future if my mom's MS status turns out to be MSS:
http://oncologypro.esmo.org/Meeting-Res ... ancer-mCRC

Of course. That regimen has been discussed extensively in different threads in this forum. We have a fellow, ACPdiddy, in that trial viewtopic.php?f=1&t=57849&p=455797
There are other similar trials ongoing. One that adds bevacizumab --Avastin-- to cobimetinib and anti PD-L1, NCT02876224; that is interesting because adds an agent that we know it is active on mCRC. Other trial for MSS NCT02060188 combines cobimetinib + anti PD-1 + anti CTLA4 --Yervoy, an already approved immuno for melanoma.

LMighty: atezolizumab/ Tecentriq is an anti PD-L1. Even if it has a slightly different mechanism of action than an anti PD-1 --as pembrolizumab/Keytruda or nivolumab/Opdivo are--, so far everything points to the fact that they have similar results.
So, the combination of Keytruda with cobimetinib --Cotellic-- or any other MEK inhibitor available in Hong Kong --like trametinib (Mekinist) should be equivalent.

Thank you so much, Maia! Very interesting info. I will definitely talk to our onc about this.

Maia wrote:So, the combination of Keytruda with cobimetinib --Cotellic-- or any other MEK inhibitor available in Hong Kong --like trametinib (Mekinist) should be equivalent.

Hi Maia,

One thing -- did you mean even though we can't get Tecentriq in Hong Kong, the combination of Keytruda with Cotellic is thought to produce similar result without Tecentriq?

LMighty wrote:One thing -- did you mean even though we can't get Tecentriq in Hong Kong, the combination of Keytruda with Cotellic is thought to produce similar result without Tecentriq?

Yes. Tecentriq (atezolizumab) is an anti PD-L1. The 'L' in the name PD-1 stands for the Ligand in the tumour cells. Keytruda (pembrolizumab) is an anti PD-1.
PD-1 is on the T cells of the immune system, PD-L1 is on the tumor cells. So both drugs release the breaks of the immune system in a same pathway, but in different 'places'. They are not the same and probably some time from now we'll learn about the particularities but, right now, clinically, all the anti PD-1 and the anti PD -L1 have demonstrated similar results. Some are ahead in the 'race' because the pharmas started testing first one instead of other, or regarding one cancer or other.
You can read a better explanation here, and watch a video --it is about a type of lung cancer, because those drugs have been first tested for that: http://cancergrace.org/lung/2016/04/20/ ... d-1_pd-l1/

There are the approved ones, for different cancers --there are many more in trials, so one always can go to a trial for an equivalent:

Anti PD- 1: Keytruda (pembrolizumab) , Opdivo (nivolumab)

Anti PD- L1: Tecentriq (atezolizumab), Bavencio (avelumab), Imfinzi (durvalumab)

---
Adding to that:
Also, there are two MEK inhibitors approved, as I said, not only Cotellic --it was just that that particular trial was ran with that one.

MEK inhibitors: Cotellic (cobimetinib), Mekinist (trametinib).

Soon, others will be approved, probably: binimetinib and selumetinib.

Sorry to butt in on your post LMighty, and wishing you and your Mom all the best, I went through similar with my mother last year

Quick question for Maia, and thank you so much for all of your incredibly useful information,

As far as you understand, are PD-1 inhibitors better suited towards MSI tumors and PD-L1 likely to work better for MSS or is it as I suspect not that simple ?