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. 2021 Feb;9(2):e001945.
doi: 10.1136/jitc-2020-001945.

Ipilimumab and nivolumab/pembrolizumab in advanced hepatocellular carcinoma refractory to prior immune checkpoint inhibitors

Jeffrey Sum Lung Wong  1 , Gerry Gin Wai Kwok  1 , Vikki Tang  1 , Bryan Cho Wing Li  1 , Roland Leung  1 , Joanne Chiu  1 , Ka Wing Ma  2 , Wong Hoi She  2 , Josephine Tsang  1 , Chung Mau Lo  2 , Tan To Cheung  2 , Thomas Yau  3
Affiliations

Ipilimumab and nivolumab/pembrolizumab in advanced hepatocellular carcinoma refractory to prior immune checkpoint inhibitors

Jeffrey Sum Lung Wong et al. J Immunother Cancer. 2021 Feb.

Abstract

Background: Programmed cell death protein 1 (PD-1) pathway blockade with immune checkpoint inhibitors (ICIs) is a standard therapy in advanced hepatocellular carcinoma (HCC) nowadays. No strategies to overcome ICI resistance have been described. We aimed to evaluate the use of ipilimumab and anti-PD-1 ICIs (nivolumab or pembrolizumab) combinations in patients with advanced HCC with progression on prior ICIs.

Methods: Patients with advanced HCC with documented tumor progression on prior ICIs and subsequently received ipilimumab with nivolumab/pembrolizumab were analyzed. Objective response rate (ORR), median duration of response (DOR), time-to-progression (TTP), overall survival (OS), and treatment-related adverse events (TRAEs) were assessed.

Results: Twenty-five patients were included. The median age was 62 (range: 51-83). About 68% were of Child-Pugh (CP) Grade A and 48% had primary resistance to prior ICI. At median follow-up of 37.7 months, the ORR was 16% with a median DOR of 11.5 months (range: 2.76-30.3). Three patients achieved complete response. The median TTP was 2.96 months (95% CI: 1.61 to 4.31). Median OS was 10.9 months (95% CI: 3.99 to 17.8) and the 1 year, 2 year and 3 year survival rates were 42.4%, 32.3% and 21.6%, respectively. The ORR was 16.7% in primary resistance group and 15.4% in acquired resistance group (p=1.00). All responders were of CP A and Albumin-Bilirubin (ALBI) Grade 1 or 2. CP and ALBI Grades were significantly associated with OS (p=0.006 and p<0.001, respectively). Overall, 52% of patients experienced TRAEs and 12% experienced Grade 3 or above TRAEs.

Conclusions: Ipilimumab and nivolumab/pembrolizumab can achieve durable antitumor activity and encouraging survival outcomes with acceptable toxicity in patients with advanced HCC who had prior treatment with ICIs.

Keywords: CTLA-4 antigen; combination; drug therapy; immunotherapy; liver neoplasms; programmed cell death 1 receptor.

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Conflict of interest statement

Competing interests: TY reports receiving honoraria from Bristol-Myers Squibb and MSD. TY has a consulting or advisory role at Bristol-Myers Squibb and MSD. JC reports receiving honoraria from Bristol-Myers Squibb and has a consulting or advisory role at Bristol-Myers Squibb. JSLW, GGWK, VT, BCWL, RL, KWM, WHS, JT, CML, and TTC have nothing to disclose.

Figures

Figure 1
Figure 1
Kaplan-Meier analysis of OS. Dotted lines plot time points, percentages represent survival rates. OS, overall survival.
Figure 2
Figure 2
Kaplan-Meier analysis of OS by resistance pattern to prior ICI. Level of significance: p=0.55 (log-rank test). ICI, immune checkpoint inhibitor; OS, overall survival.
Figure 3
Figure 3
Kaplan-Meier analysis of OS by CP Grade. Level of significance: p=0.006 (log-rank test). CP, Child-Pugh; OS, overall survival.
Figure 4
Figure 4
Kaplan-Meier analysis of OS by ALBI Grade. Level of significance: p<0.001 (log-rank test). ALBI, Albumin-Bilirubin; OS, overall survival.
See this image and copyright information in PMC

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