Real-world data on microsatellite instability status in various unresectable or metastatic solid tumors

Abstract

Microsatellite instability-high (MSI-H) is an important biomarker for predicting the effect of immune checkpoint inhibitors (ICIs) on advanced solid tumors. Microsatellite instability-high is detected in various cancers, but its frequency varies by cancer type and stage. Therefore, precise frequency is required to plan ICI therapy. In this study, the results of MSI tests actually carried out in clinical practice were investigated. In total, 26 469 samples of various cancers were examined between December 2018 and November 2019 to determine whether programmed cell death-1 blockade was indicated. The results of MSI tests were obtained for 26 237 (99.1%) of these samples. The male : female ratio was 51:49 and mean age was 64.3 years. In all samples, the overall frequency of MSI-H was 3.72%. By gender, the frequency of MSI-H was higher in female patients (4.75%) than in male patients (2.62%; P < .001). A comparison by age revealed that the frequency of MSI-H was significantly higher in patients younger than 40 years of age (6.12%) and 80 years or older (5.77%) than in patients aged between 60 and 79 years (3.09%; P < .001). Microsatellite instability-high was detected in 30 cancer types. Common cancer types were: endometrial cancer, 16.85%; small intestinal cancer, 8.63%; gastric cancer, 6.74%; duodenal cancer, 5.60%; and colorectal cancer, 3.78%. Microsatellite instability-high was detected in cancer derived from a wide variety of organs. The frequency of MSI-H varied by cancer type and onset age. These data should prove especially useful when considering ICI treatment.

Keywords: PD-1 blockade; advanced solid tumor; immune checkpoint inhibitor; microsatellite instability; mismatch repair.

FIGURE 1

CONSORT flow diagram of this study. Of the 26 469 samples, 232 were excluded due to poor or insufficient sample conditions. Microsatellite instability (MSI) testing results were obtained from the remaining 26 237 samples. Success rate of tumor‐agnostic MSI testing was 99.1% and 3.72% of all tumor showed MSI‐high (MSI‐H) status. MSI‐L, microsatellite instability‐low; MSS, microsatellite stable.

FIGURE 2

Number and proportion for each tumor sample from patients with unresectable or metastatic solid tumors examined with the microsatellite instability test. HCC, hepatocellular carcinoma; NET, neuroendocrine tumor; SCLC, small‐cell lung carcinoma

FIGURE 3

Frequency of microsatellite instability‐high (MSI‐H) tumor in each generation of patients with unresectable or metastatic solid tumors. The frequency of MSI‐H was significantly higher in patients aged <40 y (6%) and 80 y or older (5.77%) compared with patients aged between 60 and 79 y (3.09%; P < .001)

FIGURE 4

Frequency of microsatellite instability‐high (MSI‐H) in each tumor type among patients with unresectable or metastatic solid tumors. A, Tumors for which the number of analyzable samples was 100 or more. B, Tumors for which the number of analyzable samples was less than 100. adeno, adenocarcinoma; NSCLC, non‐small‐cell lung carcinoma; PNET, pancreatic neuroendocrine tumor