Camrelizumab in combination with apatinib as a perioperative treatment for patients with hepatocellular carcinoma at high risk of recurrence: A prospective, single-arm, phase 2 study

4120 Background: Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide, and a rising cause of cancer-related mortality. To date, the optimal perioperative treatment strategy for HCC patients remains unclear. It is urgent to develop novel and reliable therapeutic interventions to reduce the risk of recurrence and improve survival in patients with locally advanced HCC. Methods: This prospective, exploratory, single-arm, phase 2 study enrolled patients with primary resectable HCC who had not received prior systemic therapy. Before surgery, patients received combination treatment with four cycles of camrelizumab (200 mg, Q2W) plus apatinib (250 mg, QD). Each cycle was two weeks. The feasibility of hepatic resection was assessed by radiographic imaging. After 4-8 weeks of surgery, patients continued combination therapy (camrelizumab [200 mg, Q2W] and apatinib [250 mg, QD]) for one year. Primary endpoint was major pathological response (MPR). Secondary endpoints were pathologic complete response rate (pCR), objective response rate (ORR), disease-free survival (DFS), and safety. Exploratory endpoint was microvascular invasion (MVI). This study is registered on Clinical Trials.gov, number NCT04701060. Results: Between Jan 12, 2021, and Aug 17, 2022, 31 patients with a median age of 54 years were enrolled. Among these, 21 patients (67.7%) had hepatitis B virus infection. Before surgical incision, two patients withdrew informed consent. Therefore, ORR based on RECIST 1.1 and mRECIST were 13.8% (4/29) and 48.3% (14/29), respectively. 26 patients underwent hepatic resection, R0 resection rate was 100%, 10 (38.5%) patients achieved MPR, and pCR rate was 7.7%. The reasons for patients not undergoing surgery were disease progression and serious adverse events (AEs). Among patients with MVI, M0 was found in 57.7% (15/26) patients, MI was found in 34.6% (9/26) patients, and M2 was found in 7.7% (2/26) patients. 1-year DFS rate was 77.4%, and median DFS was not reached. The most common AEs included increased aspartate aminotransferase (74.2%), increased alanine aminotransferase (70.1%), decreased platelet count (61.3%), anemia (58.1%), and decreased lymphocyte count (51.6%). Grade 4 AEs occurred in 7 of 31 patients, and there were no treatment-related deaths. Conclusions: Camrelizumab plus apatinib as a perioperative treatment is effective and tolerable in patients with HCC at high risk of recurrence. Preoperative neoadjuvant therapy has reduced the rate of MVI. Because of the short follow-up period, whether perioperative treatment can effectively reduce recurrence rates and improve long-term survival still needs further investigation. Clinical trial information: NCT04701060 .