Camrelizumab in Combination with Apatinib in Patients with Advanced Hepatocellular Carcinoma (RESCUE): A Nonrandomized, Open-label, Phase II Trial

Abstract

Purpose: We assessed the efficacy and safety of camrelizumab [an anti-programmed death (PD-1) mAb] plus apatinib (a VEGFR-2 tyrosine kinase inhibitor) in patients with advanced hepatocellular carcinoma (HCC). Patients and Methods: This nonrandomized, open-label, multicenter, phase II study enrolled patients with advanced HCC who were treatment-naïve or refractory/intolerant to first-line targeted therapy. Patients received intravenous camrelizumab 200 mg (for bodyweight ≥50 kg) or 3 mg/kg (for bodyweight <50 kg) every 2 weeks plus oral apatinib 250 mg daily. The primary endpoint was objective response rate (ORR) assessed by an independent review committee (IRC) per RECIST v1.1. Results: Seventy patients in the first-line setting and 120 patients in the second-line setting were enrolled. As of January 10, 2020, the ORR was 34.3% [24/70; 95% confidence interval (CI), 23.3–46.6] in the first-line and 22.5% (27/120; 95% CI, 15.4–31.0) in the second-line cohort per IRC. Median progression-free survival in both cohorts was 5.7 months (95% CI, 5.4–7.4) and 5.5 months (95% CI, 3.7–5.6), respectively. The 12-month survival rate was 74.7% (95% CI, 62.5–83.5) and 68.2% (95% CI, 59.0–75.7), respectively. Grade ≥3 treatment-related adverse events (TRAE) were reported in 147 (77.4%) of 190 patients, with the most common being hypertension (34.2%). Serious TRAEs occurred in 55 (28.9%) patients. Two (1.1%) treatment-related deaths occurred. Conclusions: Camrelizumab combined with apatinib showed promising efficacy and manageable safety in patients with advanced HCC in both the first-line and second-line setting. It might represent a novel treatment option for these patients. See related commentary by Pinato et al., p. 908

Safety of PD-1/PD-L1 Inhibitors Combined With Palliative Radiotherapy and Anti-Angiogenic Therapy in Advanced Hepatocellular Carcinoma

“…However, it was unclear whether radiotherapy can be safely administered to patients also receiving the PD-1/PD-L1 inhibitors and targeted therapy combination. It should be noted that the safety profile of triple therapy in this population was similar to those reported in previous studies of two-drug combination therapy (8)(9)(10). In our study, the most common TRAEs were rash, diarrhea, aspartate aminotransferase increase, alanine transaminase increase, decreased appetite, and fatigue.…”

“…Thus, atezolizumab plus bevacizumab became the new standard of first-line therapy. Furthermore, lenvatinib plus pembrolizumab and camrelizumab in combination with apatinib in HCC have also received encouraging results from a Phase 1b and 2 study, respectively ( 9 , 10 ).…”

The Efficacy and Safety of Apatinib Plus Camrelizumab in Patients With Previously Treated Advanced Biliary Tract Cancer: A Prospective Clinical Study

“…Therefore, considering the potential synergistic efficacy of targeted therapy combined with immune checkpoint inhibitor, apatinib plus camrelizumab might be a potentially effective combination for various tumors (15). For patients with advanced HCC, apatinib combined with camrelizumab achieved a 34.3% objective response as the first-line and 22.5% as the secondline therapy (16). Similar results were also observed in osteosarcoma, gastric cancer, advanced triple-negative breast cancer and a variety of other tumors (17)(18)(19).…”

“…Although camrelizumab combined with apatinib has achieved promising results in the treatment of various tumors, including hepatocellular carcinoma, osteosarcoma and triplenegative breast cancer, this regimen has not been reported in cholangiocarcinoma (16,17,19). Currently, most trials combining multitarget TKIs with PD-1 blockade for BTC are in the recruitment phase, and few studies have reported detailed results.…”

Recent Advances and Future Prospects in Immune Checkpoint (ICI)-Based Combination Therapy for Advanced HCC

“…Median PFS was 5.7 and 5.5 months, and 12-month survival rates were 74.7% and 68.2%, respectively. Grade ≥3 TRAEs occurred in 77.4% of patients [49]. Finally, the VEGF Liver 100 trial evaluated the anti-PD-L1 avelumab in combination with axitinib (VEGF receptor 1/2/3 inhibitor) in treatment-naïve advanced HCC patients [50].…”