Stereotactic body radiotherapy with continued first-line PD-1 inhibitor-based therapy as a resistance-overcoming strategy in oligoprogressive hepatocellular carcinoma: A prospective phase II clinical study
Mené sur 35 patients atteints d’un carcinome hépatocellulaire oligoprogressif (durée médiane de suivi : 24,4 mois), cet essai de phase II évalue l'intérêt, du point de vue de la survie sans progression, d'ajouter une radiothérapie stéréotaxique à un traitement de première ligne combinant inhibiteur de PD-1 (camrélizumab/sintilimab) et lenvatinib
Purpose: This prospective phase II trial (NCT06870942) aimed to evaluate whether stereotactic body radiotherapy (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).
Methods: 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 dose [BED10] ≥60 Gy) to all oligoprogressive sites while continuing their original therapy. The primary endpoint was PFS.
Results: 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% CI: 5.6–17.0). The overall response rate (ORR) and disease control rate (DCR)were 74.3% and 91.4%, respectively. The 2-year overall survival (OS) rate of 84.9%. According to ESTRO-EORTC classification, repeat oligoprogression demonstrated significantly higher median PFS (16.6 vs. 8.9 vs. 8.9 months, p<0.05) and ORR (81.5% vs. 40.0% vs. 33.3%) compared to metachronous/induced subtypes. Grade 3-4 toxicities occurred in 8.5% (3/35) of patients, although these adverse events were reversible and manageable.
Conclusions: 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 ICI-based therapy resistance through localized immunomodulation while preserving the continuity of systemic treatment.
International Journal of Radiation Oncology, Biology, Physics , résumé, 2026