Oligoprogression of Solid Tumors on Immune Checkpoint Inhibitors: The Impact of Local Ablative Radiation Therapy

The breakthrough of a limited number of clones while on immune checkpoint inhibitors (ICIs), known as oligoprogression, has been previously described. The benefit of ablative radiation therapy (RT) directed at these clones, as opposed to changing systemic therapy, is unclear. We analyzed 30 patients with advanced solid tumors, the majority of whom (23/30, 86.7%) had either hepatocellular or urothelial carcinoma, who experienced oligoprogression on ICIs and were referred for RT. In this study, oligoprogression was defined as having experienced progression at three or fewer metastatic sites outside of the brain after achieving at least stable disease on ICIs for a minimum of three months. The median time to oligoprogression was 11.1 months from the initiation of immunotherapy. 24 patients had one oligoprogressive lesion and six had two. The median radiation dose delivered was 4650 cGy in a median of five fractions. The median progression-free survival (PFS) after RT was 7.1 months, and the time to oligoprogression was not a significant predictor of PFS2. 26 patients continued on ICIs after RT. While 17 patients subsequently progressed, 15 did so at three or fewer metastatic sites and could have theoretically stood to benefit from an additional course of salvage RT to further extend the lifespan of their ICIs. Overall survival at 6, 12, and 24 months was 100.0%, 96.3%, and 82.8%, respectively. These results suggest that RT may provide a PFS benefit and extend the lifespan of ICIs in patients who experience oligoprogression. Regardless of PFS, however, overall survival in this population appears to be excellent.