Immune checkpoint inhibitors in patients with testicular cancer: A systematic review.

638 Background: Germ cell tumors (GCT) are chemosensitive neoplasms with high cure rates, even in the metastatic setting. However, a small group of these patients will present tumors refractory to chemotherapy, with a dismal prognosis and very few effective management options. Although immune checkpoint inhibitors (ICIs) are approved for use in chemotherapy-refractory GCT for those tumors with a high microsatellite instability (MSI-H/dMMR) or high tumor mutational burden (TMB-H), the evidence supporting this indication is scarce. Methods: Original research studies, conducted on patients with GCT refractory to chemotherapy treated with ICI up to December 2023 were included. Comprehensive search strategies of 5 databases and MeSH keywords were used to locate eligible literature. Study characteristics, participant demographics, and oncological outcomes were recorded. Results: A total of 13 studies (n = 106) were identified for inclusion; 5 of which corresponded to single-patient case reports, one was identified as a retrospective cohort, 6 were phase II RCTs and we included a recent abstract from the preliminary results of a phase II RCT. Most of the studies evaluated did not request biomarkers as inclusion criteria. The median overall response rate across all patients included was 3.4% (range, 0-57), versus 0% (range 0-6) in those reported in retrospective cohort and phase II studies. Progressive disease as best clinical response was reported in most patients, with 75% (range, 0-82.9) in the overall population and 82% (range, 75 -83) in patients from retrospective cohort and phase II trials. Some of the most durable clinical responses documented in this systematic review corresponded to TMB-H or MSI-H/dMMR tumors. Conclusions: Analysis from retrospective cohorts and clinical trials evaluating ICIs for the treatment of chemotherapy-refractory GCT documented a 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. Future prospective study designs should attempt to select patients by biomarkers to shed light on the determination of clinical and molecular factors that can predict response to ICIs in this scenario.