Immune-checkpoint inhibitors highly effective against microsatellite-instability-high cancers

Last Updated: 2020-05-26

By Will Boggs MD

NEW YORK (Reuters Health) - Immune-checkpoint inhibitors (ICIs) are highly effective against cancers with defects in DNA mismatch repair proteins, so-called microsatellite-instability-high (MSI-H) cancers, according to a systematic review and meta-analysis.

"Despite the low frequency of MSI-H tumors, these agents now represent established drugs in the treatment armamentarium," Dr. Fausto Petrelli of ASST Bergamo Ovest, in Treviglio, Italy, told Reuters Health by email. "Combinations with other agents or chemotherapy may represent emerging strategies shortly for the fight against these cancers."

Dr. Petrelli and colleagues evaluated the activity of different available ICIs in patients with MSI-H cancers in their in 14 studies involving a total of 939 patients. Most were phase-2 studies.

The pooled overall response rate was 41.5%, ranging from 0% in a study of high-grade glioma to 64.7% in a study of advanced gastric/gastroesophageal junction cancer, the researchers report in JAMA Oncology.

The pooled disease-control rate was 62.8% and ranged from 33% in a study of high-grade glioma to 81% in a study of colorectal cancer.

Pooled median progression-free survival was 4.3 months, and pooled median overall survival was 24 months.

Pooled overall survival rates were 75.6% at one year and 56.5% at two years.

"The problem is the duration of these responses (the studies had a median follow up of 1-2 years), but in such an advanced setting, they still are prolonged and patients are still alive at 1 and 2 years," Dr. Petrelli said.

In subgroup analysis, overall response rates were highest for gastric cancer (61.2%) and lower for colorectal cancer (47.1%), endometrial cancer (36.1%), and other tumors (35.5%).

"I think that in many cancers where there are limited therapeutic options, or at diagnosis, as in colorectal and endometrial cancers that are the more frequently unstable tumors, a simple molecular and/or IHC (immunohistochemistry) test to determine MSI status is suggested," Dr. Petrelli said.

"Recent studies support the notion that immune-checkpoint inhibitors may be used as upfront therapy (e.g., neoadjuvant) with impressive results," he added. "In these cases, ICIs outperform standard therapies and may avoid the use of cytotoxics."

SOURCE: https://bit.ly/36rAawJ JAMA Oncology, online May 14, 2020.