Incidence of microsatellite instability-high hepatocellular carcinoma among Japanese patients and response to pembrolizumab.

AIM: Pembrolizumab has been quickly approved in many countries for the treatment of patients with unresectable or metastatic, microsatellite instability-high (MSI-H) solid tumors, which have progressed following previous treatment and who have no satisfactory alternative treatment options. We aimed to determine the incidence of MSI-H tumors in Japanese patients with advanced hepatocellular carcinoma (HCC). METHODS: We investigated the incidence of MSI-H tumors in 82 consecutive Japanese patients with unresectable HCC that had progressed after standard of care treatment. Using a companion diagnostic sequencing kit (polymerase chain reaction analysis of five microsatellite markers: BAT25, BAT26, NR21, NR24 and MONO27), we analyzed 49 biopsy specimens and 33 resection specimens. Responses to pembrolizumab were assessed with the modified Response Evaluation Criteria in Solid Tumors. RESULTS: MSI-H tumors were found in only two patients (2.4%), in whom all five markers showed slight shortening. One patient had a complete response to pembrolizumab for over 10 months, and the other was a non-responder. CONCLUSIONS: MSI-H tumor status was found in only two of 82 (2.4%) Japanese patients with advanced HCC, one of whom had a complete response to pembrolizumab. Thus, MSI status should be assessed in patients with HCC who progress after standard of care treatment.

Complete response to pembrolizumab in advanced hepatocellular carcinoma with microsatellite instability.

Hepatocellular carcinoma (HCC) has limited systemic treatment options and a poor prognosis. The immune checkpoint inhibitor pembrolizumab was recently approved for the treatment of solid tumors with microsatellite instability (MSI). However, its clinical utility for the management of HCC remains to be clarified. Here, we present a case of unresectable HCC with MSI that showed an impressive response to pembrolizumab treatment. A 64-year-old man with chronic HCV infection was diagnosed with a large HCC. His severe liver dysfunction and poor performance status prevented any treatment option other than sorafenib. However, sorafenib failed after a few days due to the rapid progression of the tumor. Based on the finding of MSI in a biopsy specimen, immunotherapy using pembrolizumab was initiated. A dramatic improvement in his general condition and a reduction in tumor size were observed after the initiation of pembrolizumab treatment. Among a cohort of 50 consecutive patients with advanced HCC who were refractory to standard systemic therapy, MSI was found only in the present case. Immune checkpoint blockade therapy induced prominent anti-tumor effects in HCC with MSI. Screening for defects in DNA mismatch repair function may be warranted in HCC patients despite the low frequency of MSI.