Camrelizumab and Apatinib Shows Long-Term OS Benefit in Advanced HCC

The combination of camrelizumab and apatinib has shown long-term survival benefit in patients with advanced hepatocellular carcinoma (HCC), according to updated results from the RESCUE (NCT03463876) trial which were presented during the 2021 American Society of Clinical Oncology Annual Meeting.

For patients with advanced, unresectable HCC, the 5-year-survival probability is approximately 10% to 18%. Checkpoint inhibitor monotherapy has only shown limited efficacy in this population. However, research suggests that the combination of a checkpoint inhibitor and an anti-angiogenic agent may prove an effective treatment strategy for different cancer types.

The RESCUE study wanted to determine if this combination was effective in advanced HCC. It is a phase 2, non-randomized, multicenter, open-label study conducted in 25 centers across China. The primary outcome of the study is objective response rate. Secondary outcomes include duration of response, disease control rate, time to objective response, 9-month survival rate, 12-month survival rate, overall survival (OS), progression-free survival (PFS), and safety as measured by the rate of adverse events.

The study is composed of a single arm. All patients received 250 mg of apatinib orally every day and 200 mg of camrelizumab intravenously every 2 weeks. Underweight patients received 3mg/kg of camrelizumab.

In order to participate, patients had to be at least 18 years old, have a confirmed clinical diagnosis of HCC with at least 1 measurable lesion, liver function status Child-Pugh Class A, Barcelona Clinic Liver Cancer stage Category B or C, failure or intolerance to prior treatment with targeted therapy, an ECOG performance status of 0 or 1, a life expectancy of at least 12 weeks, and adequate bone marrow, liver, and renal function. Patients with any active autoimmune disease, concurrent medical conditions that require the use of immunosuppressives, clinical symptoms of ascites, uncontrolled hypertension, or has bone metastases, among others, are not eligible to participate.

Between the period of March 13, 2018, and January 3, 2019, patients were assigned to 1 of 2 cohorts. Cohort 1 made up 70 patients who were enrolled during their first-line of treatment. Cohort 2 made up 120 who were enrolled during their second-line of treatment. All received the study treatment. At baseline, 88.6% pf patients in the first-line cohort and 88.3% of patients in the second-line cohort had an HBV infection.

In the first-line cohort, the median age was 53 years and 90% were male. In the second-line cohort, the median age was 51 years and 88.3% of patients were male. Additionally, 65.7% had an ECOG score of 0 and 34.3% had an ECOG score of 1 in the first-line cohort. In the second-line cohort, 56.7% had an ECOG score of 0 and 43.3% had an ECOG score of 1. In the first-line cohort, 68.6% of patients had extrahepatic metastases. In the second-line cohort, 75.8% had extrahepatic metastases. Muscular invasion was present in 28.6% of patients in the first-line cohort and 24.2% in the second-line cohort. Additionally, a-fetoprotein concentration of less than 400ng/mL occurred in 48% of patents in the first-line cohort and 50% of patients in the second-line cohort. A-fetoprotein concentration of 400ng/mL or more occurred in 50% of patients in the first-line cohort and 48.3% in the second-line cohort. 

Of the patients in cohort 1, 67.1% had received previous surgery, 17.1% had received radiotherapy, 62.9% had received interventional therapy, and 30% received local ablation. In the second-line cohort, 83.3% had received prior surgery, 26.7% had received radiotherapy, 77.5% had received interventional therapy, and 35.8% received local ablation.

At the January 3, 2021 cutoff, the median follow-up was 19.8 months in the first-line cohort and 21.7 months in the second-line cohort. The death rate in cohort 1 was 58.6% and 60% in cohort 2. For the first-line cohort, the median OS was 20.1 months (95% CI, 14.9 to not assessed), and the Kaplan-Meier estimated 24-month OS was 43.3% (95% CI, 31.3-54.7). In the second-line cohort, the median OS was 21.8 months (95% CI, 17.3-26.8%), and the 24-month OS rate was 44.6% (95% CI, 35.5-53.3).

An international, phase 3, randomized, open-label study (NCT03764293) is currently underway to test the safety and efficacy of the combination against sorafenib (Nexavar) as a first-line therapy for patients with advanced HCC. 

_REFERENCE:

_{Zhang, Y, Xu J, Shen J, et al. Update on overall survival (OS) of RESCUE: An open-label, phase 2 trial of camrelizumab (C) in combination with apatinib (A) in patients with advanced hepatocellular carcinoma (HCC). J Clin Oncol. 2021; 39(15):4076. doiI: 10.1200/JCO.2021.39.15_suppl.4076.}