News for MSI-H Jan 24 ASCO GI2017: Nivolumab New Standard

[Maia]

News | January 24, 2017 | ASCO 2017 Gastrointestinal Cancers Symposium.
Nivolumab [immunotherapy] New Standard for Previously Treated MSI-H Metastatic CRC.

"The immune checkpoint inhibitor nivolumab showed durable responses and disease control in a group of heavily pretreated patients with DNA mismatch repair deficient/microsatellite instability high (MSI-H) metastatic colorectal cancer, according to updated results from the CheckMate 142 study (abstract 519) [...]

"“Nivolumab monotherapy provided durable responses, disease control, and long-term survival in patients with MSI-H metastatic CRC,” said Michael J. Overman, MD, of the University of Texas MD Anderson Cancer Center. “Responses were observed regardless of tumor or immune cell PD-L1 expression, regardless of BRAF or KRAS mutation status, and regardless of clinical history of Lynch syndrome.”

"[...] about 4% of patients with metastatic colorectal cancer have a high degree of microsatellite instability due to a deficiency in the DNA mismatch repair system. These patients may be less responsive to conventional chemotherapy than patients who are mismatch repair proficient, and their disease is associated with elevated levels of tumor neoantigens, and tumor-infiltrating lymphocytes, and have upregulated expression of checkpoint regulators in immune cells.
"“These results suggest that nivolumab should be considered a new standard of care for patients with previously treated MSI-H advanced CRC,” Overman said. “This is in line with the recent amendment to NCCN guidelines which recommend all metastatic colorectal cancer patients have testing for MSI-H and also patients with MSI-H colorectal cancer after initial therapy be considered for either pembrolizumab or nivolumab monotherapy.”"

More: http://www.cancernetwork.com/asco-2017- ... static-crc

MS= MicroSatellite
MSS = MicroSatellite Stable (or also "repair PROeficient)
MSI = MicroSatellite Instable (or also "repair DEeficient) MSI-H = microsatellite instable High,

[plastikos]

Thanks for sharing this Maia. Good news.

[Maia]

Good news indeed, for the luckier amongst the un-luck (the MSI-H) ; )
You will love listening to Dr Venook, then (this weekend too) viewtopic.php?f=1&t=57011#p450691

[TXLiz]

Thank you Maia for posting this info. MSI high here, and will def be filing this info away for my future with our unwanted buddy, CRC.

[Maia]

I so hope you can go for it and you're one of those wonderful responders!

Check our mate Stephen (Lynch, MSI Higg), who went for a similar checkpoint inhibitor (atezolizumab, when it had not even such name) plus Avastin, in the frame of a clinical trial, all the thread viewtopic.php?f=1&t=51990

http://www.theanswertocancer.org/immuno ... es/stephen

[TXLiz]

Thanks for posting the thread about Stephen! It's really awesome to see someone fighting this disease with new drugs and therapies!!

I know I have mentioned before that I go back to MD Anderson in April and will see their genetic team. I will def relate any info they give me about this. I will be receiving my follow up CT scan and any other follow up testing to determine what folfox did for me, as I will be done with chemo in March. They have my tests and appointments scheduled. I have a bit of hope that immunotherapy might be a path for me and others. I have a lot of poor prognosticators- bowel obstruction, perineural and lymphatic invasion, right sided tumor, etc.

My good wishes and thanks to you and all of us here.

[Maia]

A the MD Anderson, they have (not recruiting yet) a very interesting trial (even for those MSS): a cancer stem cells inhibitor + checkpoint inhibitor
https://clinicaltrials.gov/ct2/show/NCT02467361

It's a many locations, in fact. The cancer stem cells inhibitor, BBI608, is already a well know drug, which demonstrates results for CRC since time ago (2012). If you look for it, you'll see several Phase II and III trials ongoing with it, in different combinations, with chemos also. So, having this one AND a checkpoint inhibitor looks most than promising, for MSI-High.