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

Abstract

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.

Procedural interventions for oligoprogression during treatment with immune checkpoint blockade in gynecologic malignancies: a case series

“…Although systemic therapy treatments varied after the procedure, most patients had a total immune checkpoint therapy length between 6 and 12 months. Our results are similar to published data demonstrating that time to oligoprogression is not a significant predictor of progression-free survival after local therapy, 25 suggesting that procedural interventions may benefit even patients with biologically more aggressive disease.…”

“…12 In a separate study of oligoprogressive lesions in a heterogeneous cohort of solid tumors treated with immune checkpoint blockade, ablative radiation therapy was found to be feasible and resulted in a median progression-free survival of 7.1 months and a 1-year overall survival rate >96%. 25 Most patients in the study continued immune checkpoint therapy after radiation therapy, and at second Original research progression, 15 of 17 patients did so at three or fewer metastatic sites and could have benefitted from additional salvage radiation therapy to further extend the lifespan of immune checkpoint blockade treatment.…”

Benefit assessment of extended dosing in cancer patients after their withdrawal from clinical trials

“…In a study conducted by Xu Q et al ( Spry et al, 2018 ), the addition of local ablation therapy to EGFR-TKI demonstrated a satisfactory survival benefit for patients with EGFR-mutated NSCLC who experienced oligoprogression during their first-line EGFR-TKI therapy ( Jiang et al, 2019 ). Similarly, radiotherapy has the potential to improve progression-free survival (PFS) and prolong the efficacy of immune checkpoint inhibitors in patients experiencing oligoprogression ( Sindhu et al, 2022 ). Similar to our findings, these studies indicate that in certain scenarios, patients with advanced disease may still respond well to their previous treatment regimen.…”

Correspondence to editorial on “Sorafenib vs. Lenvatinib in advanced hepatocellular carcinoma after atezolizumab/bevacizumab failure: A real-world study”

“…Sindhu et al analyzed 16 patients with HCC who received stereotactic body radiation therapy (SBRT) after oligoprogression during ICI therapy. 14 PFS after SBRT was 7.1 months, with 1year OS was 96.3%. There's an ongoing phase II study of sintilimab plus bevacizumab combined with radiotherapy as first-line treatment for HCC having malignant portal vein thrombi.…”