Key Takeaways & Executive Findings
- •• The combination of SHR-1210 and apatinib yielded an objective response rate of 31.1% and a disease control rate of 75.6% in advanced hepatocellular carcinoma. • Median progression-free survival was 5.8 months and median overall survival was 12.3 months, suggesting durable clinical benefit. • The safety profile was manageable, with hypertension, proteinuria, and fatigue being the most common treatment-related adverse events. • This phase II trial provides a strong rationale for a phase III randomized study of this combination in advanced HCC.
Abstract
Background: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide, and effective systemic therapies for advanced disease remain limited. This phase II, single-arm, open-label trial evaluated the efficacy and safety of SHR-1210 (a PD-1 inhibitor) combined with apatinib (a VEGFR-2 inhibitor) in patients with advanced HCC who had failed or were intolerant to prior systemic therapy. Methods: Patients received SHR-1210 (200 mg intravenously every 2 weeks) plus apatinib (250 mg orally once daily) until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR) per RECIST 1.1. Secondary endpoints included disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety. Results: Between January 2019 and December 2020, 45 patients were enrolled. The ORR was 31.1% (95% CI, 18.2-46.6), and the DCR was 75.6% (95% CI, 60.5-87.1). The median PFS was 5.8 months (95% CI, 4.2-7.4), and the median OS was 12.3 months (95% CI, 9.8-15.2). Treatment-related adverse events (TRAEs) occurred in 95.6% of patients, with the most common being hypertension (48.9%), proteinuria (42.2%), and fatigue (37.8%). Grade 3 or higher TRAEs were observed in 28.9% of patients, including elevated transaminases (11.1%) and hand-foot syndrome (8.9%). No treatment-related deaths occurred. Conclusion: SHR-1210 combined with apatinib demonstrated promising antitumor activity and a manageable safety profile in patients with advanced HCC, warranting further investigation in randomized controlled trials.
1. Introduction
Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and a leading cause of cancer-related death worldwide. Despite advances in surgical resection, liver transplantation, and locoregional therapies, the majority of patients present with advanced disease not amenable to curative treatments. Systemic therapy options have historically been limited, with sorafenib being the standard of care for over a decade. However, the emergence of immune checkpoint inhibitors and anti-angiogenic agents has revolutionized the treatment landscape of advanced HCC, offering new hope for improved outcomes.
The programmed death-1 (PD-1) inhibitor SHR-1210 has shown promising antitumor activity in various solid tumors, including HCC. Apatinib, a selective vascular endothelial growth factor receptor-2 (VEGFR-2) inhibitor, has demonstrated efficacy in gastric cancer and other malignancies. Preclinical and clinical evidence suggests that combining PD-1 inhibitors with anti-angiogenic agents may synergistically enhance antitumor immunity by modulating the tumor microenvironment. This phase II trial was designed to evaluate the efficacy and safety of SHR-1210 plus apatinib in patients with advanced HCC who had failed or were intolerant to prior systemic therapy.
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ZHANG Wei, LI Ming, WANG Fang, CHEN Jing, LIU Yang, ZHAO Lei, SUN Hong, ZHOU Qiang, WU Tao, XU Lin (2026). Efficacy and Safety of SHR-1210 Combined with Apatinib in the Treatment of Advanced Hepatocellular Carcinoma: A Single-Arm, Open-Label, Phase II Clinical Trial. Chinese Journal of New Drugs. https://doi.org/pub_80__articleID_430
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Frequently Asked Questions
What is the objective response rate of SHR-1210 combined with apatinib in advanced hepatocellular carcinoma?
The objective response rate (ORR) was 31.1% (95% CI, 18.2-46.6) as assessed by RECIST 1.1, indicating that nearly one-third of patients experienced tumor shrinkage.
What are the common adverse events associated with SHR-1210 plus apatinib?
The most common treatment-related adverse events were hypertension (48.9%), proteinuria (42.2%), and fatigue (37.8%). Grade 3 or higher adverse events occurred in 28.9% of patients, with elevated transaminases and hand-foot syndrome being the most frequent.
What is the median progression-free survival for patients treated with this combination?
The median progression-free survival (PFS) was 5.8 months (95% CI, 4.2-7.4), suggesting a meaningful delay in disease progression.
What is the median overall survival for patients treated with SHR-1210 plus apatinib?
The median overall survival (OS) was 12.3 months (95% CI, 9.8-15.2), indicating a promising survival benefit in this patient population.
Is this combination therapy safe for patients with advanced hepatocellular carcinoma?
The safety profile was manageable, with no treatment-related deaths. The most common grade 3 or higher adverse events were elevated transaminases (11.1%) and hand-foot syndrome (8.9%), which were manageable with supportive care.
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