Incidence of Microsatellite Instability in Metastatic CRC High, Tied to Worse Survival

Results from a recent study of patients with metastatic colorectal cancer (CRC) suggest that the use of immunotherapy should be considered as first-line treatment in those with microsatellite instability-high (MSI-H) tumors (Cancer Med. 2019 May 9. Epub ahead of print).

“Immunotherapy for patients with microsatellite-instable…tumors or BRAF-inhibitors combination treatment for BRAF-mutated…tumors in metastatic colorectal cancer…is promising, but the frequency of these molecular changes in trial patients are low,” said Kristine Ø. Aasebø, PhD candidate, University of Bergen, Department of Clinical Science, Faculty of Medicine, Norway, and colleagues.

“Unselected population-based studies of these molecular changes are warranted,” they added.

A total of 798 patients with metastatic CRC were included in the study, which was based in Scandinavia. Dr Aasebø and her co-investigators estimated patient and molecular tumor characteristics, overall survival (OS), and progression-free survival (PFS).

Overall, 40 (7%) of 583 tumor samples were MSI-H and 120 (20%) of 591 were BRAF-mutated; in addition, 87% of MSI-H tumors were BRAF-mutated (non-Lynch).

Patients aged >75 years were more likely to have MSI-H (10% vs 6%) and MSI-H/BRAF-mutated (9% vs 4%) tumors than those aged ≤75 years. Patients with MSI-H tumors had significantly lower response rate (5% vs 44%), PFS (4 vs 8 months), and OS (9 vs 18 months) after first-line chemotherapy than patients with microsatellite-stable tumors.

According to Dr Aasebø et al, MSI-H tumors and BRAF mutations were independent poor prognostic factors for OS (P = .049; P <.001) and PFS (P = .045; P = .005) after first-line chemotherapy.

Of note, patients with MSI-H tumors were given less second-line chemotherapy than those without MSI-H tumors (15% vs 37%; P = .005).

“In unselected m[etastatic] CRC patients, MSI-H and mutBRAF [BRAF-mutated] cases were more common than previously reported. Patients with MSI-H tumors had worse survival, less benefit from chemotherapy, and they differed considerably from recent third-line immunotherapy trial patients as they were older and most had mutBRAF tumor (non-Lynch),” Dr Aasebø and colleagues concluded.—Hina Khaliq