Regorafenib + Nivolumab - Immunotherapy might work in MSS CRC

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Rock_Robster
Posts: 375
Joined: Thu Oct 25, 2018 5:27 am
Location: Melbourne, Australia

Re: Regorafenib + Nivolumab - Immunotherapy might work in MSS CRC

Postby Rock_Robster » Mon Nov 04, 2019 6:52 pm

Wewillfight wrote:If you guys were to take a shot at one of these combos which would it be?

Stivarga/Opdivo? (REGONIVO)

Avastin/ Opdivo

Avastin or Stivarga / Pembo

Is there any indication that Avastin instead of Stivarga could be more beneificial

Obviously it is a roll of the dice but hoping to weight the dice in favour especially if throwing 20-50k at it

I’m assuming you’re MSS in this response...

I’m not aware of any suggested synergy between Avastin and Opdivo or Pembro. Obviously Avastin is a good drug so no reason not to take it, however also no reason to expect it would make a PD-1 inhibitor work in an MSS patient.

Pembro (Keytruda) and Opdivo are both PD-1 checkpoint inhibitors, so in theory Rego could have a similar sensitising effect with Keytruda that it appears to with Opdivo. There are trials underway now to test this. However given it’s currently untested and you’d be gambling with your own money, I’d personally preference Opdivo.

There are a couple of other things you could consider alongside a PD-1 inhibitor:

1) radiation therapy - there is suggestion (and several trials) that radiation to tumour areas (anywhere in the body) may sensitise the immune system to previously ‘cold’ tumour cells, allowing a PD-1 inhibitor to have therapeutic effect

2) Pixatimod - which is currently in trials with Opdivo with some very early but encouraging results.

Best of luck,
Rob
Last edited by Rock_Robster on Tue Nov 05, 2019 7:15 am, edited 1 time in total.
Male 37; Melbourne, Australia
10/2018 Dx 3.5cm RC adenocarcinoma, 12cm from AV
Mod diff, EMVI+ LVI+ PNI-
3 LN; 4 liver mets, resectable
pT3pN1aM1a; Stage IVa. MSS, NRAS (G13R)
CEA: Oct-18= 12; Nov-18= 14, Mar-19= 2.4, Aug-19 <2.0
11/18 - FOLFOX x 6
3/19 - Liver resection
4-5/19 - 25 x pelvic radiation; complete met. response, TRG 3
07/19 - ULAR (robot), temp ileo, 1/27 LN
08/19 - Missed liver spot
08-11/19 - FOLFOX x 1, FOLFOXIRI x 1, FOLFIRI x 5
12/19 - Planned liver resection #2 & stoma reversal

Pyro70
Posts: 155
Joined: Mon Jan 21, 2019 4:25 pm

Re: Regorafenib + Nivolumab - Immunotherapy might work in MSS CRC

Postby Pyro70 » Tue Nov 05, 2019 5:47 am

Wewillfight wrote:If you guys were to take a shot at one of these combos which would it be?

Stivarga/Opdivo? (REGONIVO)

Avastin/ Opdivo

Avastin or Stivarga / Pembo

Is there any indication that Avastin instead of Stivarga could be more beneificial

Obviously it is a roll of the dice but hoping to weight the dice in favour especially if throwing 20-50k at it


The data we have is most compelling for Regonivo.

However a Cape+Bev+PD1 study has hit its primary endpoint and is being explored more. I don’t really know what to make of this data because a similar trial call MODUL was negative.
https://www.targetedonc.com/news/combin ... udies-show

There was also an abstract at ASCO 2019 that showed positive results from PD1+CTLA4+radiation

One could consider combining these
Eg Regonivo+radiation
Regonivo+bevacizumab likely doesn’t make much sense because if the similarities between Ref and Bev

Pixatimod is also interesting, but likely difficult/impossible to get your hands on.
Dx Jan 2017 stage IVB w/ PC age 35
FOLFOX
SEP 17 HIPEC 1, anastamosis leak
XELODA
MAR 18 HIPEC 2
JUN 18, ileo reversal and 2nd anastamosis leak

Rock_Robster
Posts: 375
Joined: Thu Oct 25, 2018 5:27 am
Location: Melbourne, Australia

Re: Regorafenib + Nivolumab - Immunotherapy might work in MSS CRC

Postby Rock_Robster » Tue Nov 05, 2019 6:39 am

Pyro70 wrote:
Wewillfight wrote:If you guys were to take a shot at one of these combos which would it be?

Stivarga/Opdivo? (REGONIVO)

Avastin/ Opdivo

Avastin or Stivarga / Pembo

Is there any indication that Avastin instead of Stivarga could be more beneificial

Obviously it is a roll of the dice but hoping to weight the dice in favour especially if throwing 20-50k at it

Pixatimod is also interesting, but likely difficult/impossible to get your hands on.

True, unless you happen to be in Australia: https://www.anzctr.org.au/Trial/Registr ... ?id=373869
Male 37; Melbourne, Australia
10/2018 Dx 3.5cm RC adenocarcinoma, 12cm from AV
Mod diff, EMVI+ LVI+ PNI-
3 LN; 4 liver mets, resectable
pT3pN1aM1a; Stage IVa. MSS, NRAS (G13R)
CEA: Oct-18= 12; Nov-18= 14, Mar-19= 2.4, Aug-19 <2.0
11/18 - FOLFOX x 6
3/19 - Liver resection
4-5/19 - 25 x pelvic radiation; complete met. response, TRG 3
07/19 - ULAR (robot), temp ileo, 1/27 LN
08/19 - Missed liver spot
08-11/19 - FOLFOX x 1, FOLFOXIRI x 1, FOLFIRI x 5
12/19 - Planned liver resection #2 & stoma reversal

Pyro70
Posts: 155
Joined: Mon Jan 21, 2019 4:25 pm

Re: Regorafenib + Nivolumab - Immunotherapy might work in MSS CRC

Postby Pyro70 » Tue Nov 05, 2019 8:57 am

Rock_Robster wrote:
Pyro70 wrote:
Wewillfight wrote:If you guys were to take a shot at one of these combos which would it be?

Stivarga/Opdivo? (REGONIVO)

Avastin/ Opdivo

Avastin or Stivarga / Pembo

Is there any indication that Avastin instead of Stivarga could be more beneificial

Obviously it is a roll of the dice but hoping to weight the dice in favour especially if throwing 20-50k at it

Pixatimod is also interesting, but likely difficult/impossible to get your hands on.

True, unless you happen to be in Australia: https://www.anzctr.org.au/Trial/Registr ... ?id=373869



True. But you still have to get in the trial. Are you pursuing this? I’m quite disappointed on the slow pace of development of Pixatimod...
Dx Jan 2017 stage IVB w/ PC age 35
FOLFOX
SEP 17 HIPEC 1, anastamosis leak
XELODA
MAR 18 HIPEC 2
JUN 18, ileo reversal and 2nd anastamosis leak

Rock_Robster
Posts: 375
Joined: Thu Oct 25, 2018 5:27 am
Location: Melbourne, Australia

Re: Regorafenib + Nivolumab - Immunotherapy might work in MSS CRC

Postby Rock_Robster » Tue Nov 05, 2019 5:04 pm

:cry:
Pyro70 wrote:
Rock_Robster wrote:
Pyro70 wrote:True, unless you happen to be in Australia: https://www.anzctr.org.au/Trial/Registr ... ?id=373869

True. But you still have to get in the trial. Are you pursuing this? I’m quite disappointed on the slow pace of development of Pixatimod...

Quite right. I’m very interested in the drug but this trial doesn’t really line up with my treatment plan in terms of both timing and drug selection. I agree the pacing is ridiculously slow - I don’t know if they’re having issues recruiting or what (these are not small hospitals that are involved), but it’s frustrating to say the least.
Male 37; Melbourne, Australia
10/2018 Dx 3.5cm RC adenocarcinoma, 12cm from AV
Mod diff, EMVI+ LVI+ PNI-
3 LN; 4 liver mets, resectable
pT3pN1aM1a; Stage IVa. MSS, NRAS (G13R)
CEA: Oct-18= 12; Nov-18= 14, Mar-19= 2.4, Aug-19 <2.0
11/18 - FOLFOX x 6
3/19 - Liver resection
4-5/19 - 25 x pelvic radiation; complete met. response, TRG 3
07/19 - ULAR (robot), temp ileo, 1/27 LN
08/19 - Missed liver spot
08-11/19 - FOLFOX x 1, FOLFOXIRI x 1, FOLFIRI x 5
12/19 - Planned liver resection #2 & stoma reversal

boswind
Posts: 71
Joined: Fri Apr 11, 2014 12:04 pm

Re: Regorafenib + Nivolumab - Immunotherapy might work in MSS CRC

Postby boswind » Wed Nov 06, 2019 1:37 pm

Pyro70 wrote:Latest results from the Regonivo patients I’m tracking:

*Total of 8 patients had their first scan or have stopped the combo.
*2 patients have a potential response (seeing cavitation, but shrinkage isn’t at the 30% required by RECIST for an official response).
*2 patients are stable
*4 patients have died or entered hospice

One current hypothesis is that patients with a lower performance status and/or more advanced disease don’t perform as well as those that take the combo earlier.


The numbers are excellent! Thanks.
01.24.14 Male, DX @54 Rectosigmoid Cancer, MRI: T3N0M0
03.19.14 Completed 5-week Radia+Xeloda
05.07.14 Had surgery
02.25.15 CT showed stage 4.
03.15 - 08.15, folfox + Avastin
08.15 - 07.17, 5FU+leucovorin+Avastin
07.17 - 01.18, Folfuri + Avastin
02.18 - 03.19, Centuximab + Irinotecan
90 rounds of chemos received (as of 12.27.18)
MSS, KRAS wt, BRAF wt
03.19 - 05.19, Keytruda
05.19 - 9.19, Folfox+Avastin
10.22.19 - rechallenge Centuximab+Irinotecan

natelaugh
Posts: 83
Joined: Wed Apr 03, 2019 11:40 pm

Re: Regorafenib + Nivolumab - Immunotherapy might work in MSS CRC

Postby natelaugh » Wed Nov 06, 2019 1:50 pm

boswind wrote:
Pyro70 wrote:Latest results from the Regonivo patients I’m tracking:

*Total of 8 patients had their first scan or have stopped the combo.
*2 patients have a potential response (seeing cavitation, but shrinkage isn’t at the 30% required by RECIST for an official response).
*2 patients are stable
*4 patients have died or entered hospice

One current hypothesis is that patients with a lower performance status and/or more advanced disease don’t perform as well as those that take the combo earlier.


The numbers are excellent! Thanks.

Why do you consider these numbers to be good? I will be having a meeting with my dad oncologist and debate with him on this regimen but I don't know what is good or bad about these results.

Thanks,
Nate.
Caregiver to 80M
DX:CC,RC,desc
11/2018 rightPain
1/19/19 scopy,path
1/23 CTscan
2/19 surgery
2/26-2/28 NGTube
2/28-3/14 TPN bc ileus
3/2 2nd surgeryCloseOpenWound
3/4-3/28 woundVac
size: 6cm Adenocarcinoma
grade Poorly
Stage IIIC T3N2aMx
PositiveLymph:5of28
BaselineCEA:68
LVI:Y
PNI:N
Surgical margins:clear
MSI:MMR (MLH1, MSH2, MSH6, PMS2) Intact nuclear expression
Lynch status:N
Laparascopic, partial colectomy
CEA:3/28/19 2.8
Chemo:4/16/19-9/17/19 5FU,12cycles,every 14days,leucoverin,zofran,Dexamethasone

Pyro70
Posts: 155
Joined: Mon Jan 21, 2019 4:25 pm

Re: Regorafenib + Nivolumab - Immunotherapy might work in MSS CRC

Postby Pyro70 » Thu Nov 07, 2019 7:56 am

natelaugh wrote:
boswind wrote:
Pyro70 wrote:Latest results from the Regonivo patients I’m tracking:

*Total of 8 patients had their first scan or have stopped the combo.
*2 patients have a potential response (seeing cavitation, but shrinkage isn’t at the 30% required by RECIST for an official response).
*2 patients are stable
*4 patients have died or entered hospice

One current hypothesis is that patients with a lower performance status and/or more advanced disease don’t perform as well as those that take the combo earlier.


The numbers are excellent! Thanks.

Why do you consider these numbers to be good? I will be having a meeting with my dad oncologist and debate with him on this regimen but I don't know what is good or bad about these results.

Thanks,
Nate.


Nate, I agree with you. From this data it’s hard to say that Regonivo is much better than Regorafenib monotherapy. But there is some promise in the 25% that seem to have a response despite not having significant shrinkage. Hopefully with more data it will be clearer. Still 50% stability isn’t bad. For me the risk of adding nivolumab is low enough that for anyone considering starting Regorafenib they should add the IO agent.
Dx Jan 2017 stage IVB w/ PC age 35
FOLFOX
SEP 17 HIPEC 1, anastamosis leak
XELODA
MAR 18 HIPEC 2
JUN 18, ileo reversal and 2nd anastamosis leak

Wewillfight
Posts: 15
Joined: Sun Mar 03, 2019 5:27 am

Re: Regorafenib + Nivolumab - Immunotherapy might work in MSS CRC

Postby Wewillfight » Thu Nov 07, 2019 11:12 am

If there is 25% success rate from this combo that is huge. It might not sound great on the face of it by Opdivo mono-therapy had less than 5% efficacy in MSS patients. This gives patients a big boost
40 y/o
Diag Nov 2016 stage IIIc, surgery, colostomy, 2 lymph involved
6 months FOLFOX
NED
Nov 2018 recurrence , surgery , some spread to pertineum
Jan-June 2019 Folfiri+Cetux
Clear scans
August 2019: small bowel inflammation, partial blockage symptoms

Pyro70
Posts: 155
Joined: Mon Jan 21, 2019 4:25 pm

Re: Regorafenib + Nivolumab - Immunotherapy might work in MSS CRC

Postby Pyro70 » Thu Nov 07, 2019 8:26 pm

Wewillfight wrote:If there is 25% success rate from this combo that is huge. It might not sound great on the face of it by Opdivo mono-therapy had less than 5% efficacy in MSS patients. This gives patients a big boost


Well the disease control rate is closer to 50%. The question is how does this compare to Regorafenib monotherapy? Unless we see actual responses it’s unclear if the IO component is helping (without a large trial using a Regorafenib control group). Currently the ORR is technically 0% based on RECIST despite some patients clearly benefiting. But we don’t know if they would have benefited anyways on Regorafenib monotherapy.
Dx Jan 2017 stage IVB w/ PC age 35
FOLFOX
SEP 17 HIPEC 1, anastamosis leak
XELODA
MAR 18 HIPEC 2
JUN 18, ileo reversal and 2nd anastamosis leak

natelaugh
Posts: 83
Joined: Wed Apr 03, 2019 11:40 pm

Re: Regorafenib + Nivolumab - Immunotherapy might work in MSS CRC

Postby natelaugh » Thu Nov 07, 2019 8:47 pm

Pyro70 wrote:
Wewillfight wrote:If there is 25% success rate from this combo that is huge. It might not sound great on the face of it by Opdivo mono-therapy had less than 5% efficacy in MSS patients. This gives patients a big boost


Well the disease control rate is closer to 50%. The question is how does this compare to Regorafenib monotherapy? Unless we see actual responses it’s unclear if the IO component is helping (without a large trial using a Regorafenib control group). Currently the ORR is technically 0% based on RECIST despite some patients clearly benefiting. But we don’t know if they would have benefited anyways on Regorafenib monotherapy.


My first discussion about regonivo regimen with my dad oncologist, he stated the exact thing. "Don't know result with only Regorafenib monotherapy." I had no response because no data.

Nate.
Caregiver to 80M
DX:CC,RC,desc
11/2018 rightPain
1/19/19 scopy,path
1/23 CTscan
2/19 surgery
2/26-2/28 NGTube
2/28-3/14 TPN bc ileus
3/2 2nd surgeryCloseOpenWound
3/4-3/28 woundVac
size: 6cm Adenocarcinoma
grade Poorly
Stage IIIC T3N2aMx
PositiveLymph:5of28
BaselineCEA:68
LVI:Y
PNI:N
Surgical margins:clear
MSI:MMR (MLH1, MSH2, MSH6, PMS2) Intact nuclear expression
Lynch status:N
Laparascopic, partial colectomy
CEA:3/28/19 2.8
Chemo:4/16/19-9/17/19 5FU,12cycles,every 14days,leucoverin,zofran,Dexamethasone


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