Stereotactic Body Radiation Therapy With Continued First-Line PD-1 Inhibitor-based Therapy as a Resistance-Overcoming...

This prospective phase 2 trial (NCT06870942) aimed to evaluate whether stereotactic body radiation therapy (SBRT) combined with continued first-line PD-1 inhibitor-based therapy could overcome acquired resistance and prolong progression-free survival (PFS) in patients with oligoprogressive hepatocellular carcinoma (HCC).

Patients with oligoprogressive HCC (≤5 lesions, ≤3 organs) of first-line PD-1 inhibitor therapy (camrelizumab/sintilimab) combined with lenvatinib were enrolled. Participants received tumor-directed SBRT (biologically effective dose₁₀ ≥ 60 Gy) to all oligoprogressive sites while continuing their original therapy. The primary endpoint was PFS.

Thirty-five eligible patients were recruited between July 2022 and March 2023, with a median follow-up of 24.4 months. The primary endpoint was met, with a median PFS of 11.3 months (95% confidence interval, 5.6-17.0). The overall response rate (ORR) and disease control rate were 74.3% and 91.4%, respectively. The 2-year overall survival (OS) rate was 84.9%. According to the European Society for Radiotherapy and Oncology and European Organisation for Research and Treatment of Cancer (ESTRO-EORTC) classification, repeat oligoprogression demonstrated significantly higher median PFS (16.6 vs 8.9 vs 8.9 months; P < .05) and ORR (81.5% vs 40.0% vs 33.3%) compared with metachronous/induced subtypes. Grade 3-4 toxicities occurred in 8.5% (3/35) of patients, although these adverse events were reversible and manageable.

SBRT augmentation of frontline PD-1 inhibitor-based therapy enabled significant prolongation of PFS in oligoprogressive HCC with a favorable safety profile. This strategy may overcome acquired immune checkpoint inhibitor-based therapy resistance through localized immunomodulation while preserving the continuity of systemic treatment.