Sintilimab (PD-1 inhibitor) plus lenvatinib as conversion therapy followed by sequential surgery (SILENSES) for advanced unresectable hepatocellular carcinoma: a phase II, expansion trial.
Our previous findings demonstrated the promising antitumor activity and manageable safety of sintilimab-lenvatinib conversion therapy. The current study aimed to evaluate long-term survival outcomes in patients with unresectable hepatocellular carcinoma (HCC) who underwent sequential surgical resection after successful conversion therapy. In this prospective, single-arm, expansion, phase II trial, patients with unresectable HCC received lenvatinib plus sintilimab conversion therapy. Hepatectomy was performed in consenting patients after successful conversion therapy. The primary endpoint was the conversion rate; secondary endpoints included median overall survival (OS), 5-year survival rates, and recurrence-free survival (RFS). Successful conversion was achieved in 67 of 120 patients (56%, 67/120). Independent imaging review per mRECIST and RECIST v1.1 criteria demonstrated objective response rates of 58.3% (70/120) and 45.8% (55/120), respectively. With a median follow-up of 41.0 months (95% confidence interval [CI], 39.5-42.5) for the entire cohort, the median OS was 36.0 months (95% CI, 25.0 to not estimable [NE]), with a 5-year OS rate of 42.6% (95% CI, 34.0-53.0). Following multidisciplinary team evaluation and consideration of patient preferences, 60 patients underwent surgical resection, achieving a median RFS of 40.0 months (95% CI, 24.0 to NE) and a 5-year survival rate of 73.9% (95% CI, 62.7-87.1). Grade ≥3 treatment-related adverse events occurred in 37 patients (31%). Approximately half of the patients with unresectable HCC achieved successful conversion after sintilimab plus lenvatinib therapy. Among those who achieved successful conversion, subsequent curative surgery demonstrated not only a favorable safety profile but also significant survival benefits. Trial registration number: ChiCTR1900023914.
Authors
Lu Lu, Zhang Zhang, Li Li, Zhang Zhang, Hu Hu, Li Li, Cao Cao, Wang Wang, Wang Wang, Ye Ye, Qu Qu, Li Li, Ma Ma, Wan Wan, Liu Liu, Liu Liu, Xu Xu, Tang Tang, Zhao Zhao, Pan Pan, Yang Yang, Yuan Yuan, Chen Chen, Bian Bian
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