A Phase 2 Study of Camrelizumab for Advanced Hepatocellular Carcinoma: Two-Year Outcomes and Continued Treatment beyond First RECIST-Defined Progression

Abstract

<b><i>Introduction:</i></b> In a multicenter, open-label, parallel-group, randomized, phase 2 study for pretreated advanced hepatocellular carcinoma (HCC), camrelizumab showed potent antitumor activity and acceptable safety profile. The aim of this report was to provide long-term data and evaluate potential benefit of treatment with camrelizumab beyond progression. <b><i>Methods:</i></b> From November 15, 2016, to November 16, 2017, 217 patients received camrelizumab 3 mg/kg intravenously every 2 or 3 weeks. Treatment beyond first Response Evaluation Criteria in Solid Tumors (RECIST)-defined progression (TBP) with camrelizumab was allowed. <b><i>Results:</i></b> At data cutoff of December 16, 2019 (>2 years after the last patient enrollment; median duration of follow-up, 13.2 months [IQR 5.7–25.8]), 14 (43.8%) of the 32 responses per blinded independent central review were ongoing. The median duration of response was not reached (range 2.5–30.5 + months). The ongoing response rates at 12, 18, and 24 months were 68.3% (95% confidence interval [CI] 47.7–82.2), 59.8% (95% CI 38.8–75.6), and 53.1% (95% CI 31.0–71.0), respectively. The median overall survival (OS) was 14.2 months (95% CI 11.5–16.3). The 18- and 24-month OS rates were 41.3% (95% CI 34.6–47.9) and 33.7% (95% CI 27.3–40.2), respectively. Of the 172 patients who experienced RECIST-defined progression per investigator, 102 received TBP, while 70 did not (non-TBP). The median OS was 16.9 months (95% CI 13.3–22.6) in the TBP group versus 9.4 months (95% CI 5.8–14.8) in the non-TBP group, and the 18- and 24-month OS rates were 47.5% (95% CI 37.3–56.9) versus 33.1% (95% CI 22.3–44.3) and 38.8% (95% CI 29.2–48.4) versus 23.2% (95% CI 13.8–34.1), respectively. No new safety signals of camrelizumab were observed. <b><i>Conclusions:</i></b> With prolonged follow-up, camrelizumab continues to demonstrate the durable response and long survival in pretreated advanced HCC patients with manageable toxicities, especially in those who continued the treatment beyond first RECIST-defined progression.

Microwave ablation and synchronous transarterial chemoembolization combined with PD-1 inhibitor in patients with hepatocellular carcinoma following tyrosine kinase inhibitor intolerance

“…Our study suggested that MWA-TACE combined with PD-1 inhibitor was safe for the treatment of TKI-intolerant HCC patients. The most common AEs related to PD-1 inhibitor were similar to those reported in previous studies ( 32 , 33 ). In addition, the MWA and TACE procedures were well tolerated and manageable, suggesting that the combination therapy does not increase the AEs related to MWA-TACE.…”

Identification on surrogating overall survival with progression-free survival of first-line immunochemotherapy in advanced esophageal squamous cell carcinoma—an exploration of surrogate endpoint

“…In our retrospective observational cohort, patients who continued PD-1/PD-L1 inhibitors treatment after progression had a longer PPS and lower annual risk of death than patients who did not. Following the first progression of their disease, patients obtained a long-term remissions to treatment and longer survival with continued immunotherapy in advanced melanoma [ 19 ], advanced hepatocellular carcinoma [ 20 ], and advanced gastric cancer [ 18 ]. Patients experience abnormal responses to inhibitors of PD-1/PD-L1 and an inflammatory reaction to immune checkpoint treatment might be confused with PD in radiographical assessments [ 43 ]; therefore, it might not be appropriate to cease treatment as soon as the tumor appears to have progressed if there are no adverse effects of the current treatment on the patient.…”

“…However, meta-analyses of immunotherapy-based trials revealed that the PFS-assessed treatment effect correlated only poorly or moderately with OS, and the ongoing use of PFS as a surrogate endpoint (SE) in the immunotherapy era was questioned [ 16 , 17 ]. In addition, the long-term efficacy of immunotherapy means the post-progression survival (PPS) tended to improve and treatment beyond progression (TBP) could confer a survival benefit in patients treated using inhibitors of PD-1/PD-L1 [ 18 – 20 ]. Herein, we aimed to determine if PFS can be employed as an OS surrogate in advanced ESCC patients treated using first-line immunochemotherapy, and to study PPS and the risk of death after progressive disease (PD) in patients who received immunochemotherapy, aiming to guide future PD-1 research and clinical practice.…”

Identifying Patients at Risk of Acute Kidney Injury among Patients Receiving Immune Checkpoint Inhibitors: A Machine Learning Approach

“…Cancer of the liver and biliary system is one of the common refractory cancers, and it has a strong immune-mediated pathogenesis that allows ICPi to exert significant antitumor effects and become an effective alternative after sorafenib treatment failure. Pembrolizumab, camrelizumab and tislelizumab are also recommended as second-line regimens for hepatocellular carcinoma in several guidelines [ 34 , 35 , 36 ]. Gastrointestinal tract cancer is a global health problem, and prospective research results support the use of ICPis in the third-line treatment of advanced gastric cancer [ 37 , 38 , 39 ].…”