Immune Checkpoint Inhibitors in Patients with Testicular Cancer: A Systematic Review

Germ cell tumors (GCTs) are chemosensitive neoplasms with high cure rates; however, a small group of patients present tumors with refractory chemotherapy, with a dismal prognosis and few effective management options. Although immune checkpoint inhibitors (ICIs) are approved for use in chemotherapy refractory GCT, the evidence supporting this indication remains scarce. Original research studies were included on patients with GCTs refractory to chemotherapy treated with ICI up to December 2023. Comprehensive search strategies databases and MeSH keywords were used to locate eligible literature. Study characteristics, participant demographics, and oncological outcomes were recorded. A total of 13 studies (n = 106) were included, five single-patient case reports, one retrospective cohort, six-phase II randomized controlled trials (RCTs), and an abstract from the preliminary results of a phase II RCT. Most of the studies evaluated did not request biomarkers as inclusion criteria. Median overall response rate across studies was 3.4% (range, 0-57) and 0% (range, 0-6) in retrospective cohort and phase II studies. Progressive disease as the best response was present in most patients, with 75% (range, 0-82.9) in the overall population and 82% (range, 75 -83) in the retrospective cohort and phase II trials. Some of the most durable clinical responses documented in this systematic review corresponded to high tumor mutational burden (TMB-H) or high microsatellite instability (MSI-H)/dMMR tumors. Retrospective cohorts and clinical trials evaluating ICIs for the treatment of chemo-refractory GCTs documented limited activity of these drugs as a single intervention in patients not selected by biomarkers, with a tendency to better results described in those with TMB-H or MSI-H/dMMR tumors.