CheckMate 040 subanalysis shows nivolumab and high-dose ipilimumab of benefit in Asian HCC patients and overall population

Combination immunotherapy with nivolumab (1 mg/kg) and high-dose ipilimumab (3 mg/kg), given every 3 weeks (nivo1+ipi3 Q3W) for four cycles, followed by flat-dose nivolumab (240 mg) maintenance every 2 weeks (Q2W), achieved greater efficacy vs two high-dose nivolumab (3 mg/kg) and ipilimumab (1 mg/kg) regimens (nivo3+ipi1) in patients with advanced hepatocellular carcinoma (HCC) and in Asian patients, in particular, according to a subanalysis of the phase I/II CheckMate 040 trial presented at the virtual World Congress on Gastrointestinal Cancer (WCGC) 2020.

“Chronic hepatitis B is a risk factor for HCC and has a higher incidence in Asia vs non-Asian regions,” stated first author, Dr Thomas Yau of the Department of Medicine, University of Hong Kong. [WHO, Global Hepatitis Report, 2017; Cancer 2016;122:3430-3046] “As a result, Eastern and Southeast Asian regions have some of the highest global incidence of HCC.” [CA Cancer J Clin 2018;68:394-424]

Across the three arms of the trial (arm A: nivo1+ipi3 Q3W, followed by nivolumab 240 mg Q2W; arm B: nivo3+ipi1 Q3W, followed by nivolumab 240 mg Q2W; arm C: nivo3 Q2W + ipi1 Q6W), Asian (Chinese, Japanese and Korean) patients comprised 55 percent to 74 percent of overall population. [Yau T et al, WCGC 2020, abstract O-5]

“A higher proportion of Asian patients had received more lines of prior systemic therapy and prior local treatment vs the overall population,” noted Yau. Between 19 percent and 28 percent of Asian patients had received two lines of prior therapy, vs between 10 percent and 22 percent of the overall population. Between 7 percent and 22 percent of Asian patients had received three or more lines of therapy before participating in the trial, vs 4 percent to 14 percent of the overall population. While the majority of all patients had received local treatment (58–67 percent), this proportion was higher among Asian patients (69–74 percent).

The most common reason for treatment discontinuation was disease progression as opposed to study-drug toxicity or other reasons. “Discontinuation due to disease progression was the lowest in arm A in both the Asian subpopulation [arm A: 61 percent; arm B: 74 percent; arm C: 72 percent] and the overall population [arm A: 51 percent; arm B: 69 percent; arm C: 69 percent],” highlighted Yau.

In addition, arm A had longer median overall survival (OS) in both populations; Asian patients in arm A achieved a median OS of 16.4 months, while the median OS in the overall population was 22.8 months. Median OS varied between 11.2 months and 12.7 months in the other arms in the overall and Asian populations.

The rate of grade 3/4 treatment-related adverse events (TRAEs) was the highest in arm A among both Asian patients (52 percent) and in the overall population (53 percent), vs 26–31 percent in the other arms. However, hepatic TRAEs such as alanine aminotransferase and aspartate aminotransferase level increases were comparable between both populations across treatment arms. Among immune-mediated adverse events (IMAEs), rash, hepatitis and adrenal insufficiency were the most common and were particularly prevalent among Asian patients in arm A.

“Small differences between the two populations may be related to the small sample size or variation in baseline aetiology,” commented Yau. “Most IMAEs were manageable and resolved using established management algorithms.”