Immune‐related adverse events predict responses to <scp>PD</scp>‐1 blockade immunotherapy in hepatocellular carcinoma

Lu, Lianghe; Xing, Kaili; Wei, Wei; Ling, Yihong; Li, Peng; Li, Shaohua; Wang, Yan; Xie, Dan; Guo, Rong; Cai, Mengli

doi:10.1002/ijc.33609

Cited by 18 publications

(14 citation statements)

References 29 publications

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“…In contrast to the above, no difference in serious adverse events was investigated between the TACE and no-TACE groups, which was the same result as in other reports (25,26), indicating the safety of this therapeutic combination. Furthermore, skin rash was reported as a common adverse event with both PD-1 inhibitors and TKIs as tumor therapy, so the treatment response might be related to rash (32), which is consistent with our results.…”

Section: Discussionsupporting

confidence: 92%

The efficacy and safety of conventional transcatheter arterial chemoembolization combined with PD-1 inhibitor and anti-angiogenesis tyrosine kinase inhibitor treatment for patients with unresectable hepatocellular carcinoma: a real-world comparative study

Guo

Zhu²,

Zhang³

et al. 2022

Front. Oncol.

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AimWe sought to evaluate the efficacy and safety of conventional transcatheter arterial chemoembolization (cTACE) sequentially combined with systemic treatment by programmed cell death protein 1 (PD-1) inhibitor and anti-angiogenesis tyrosine kinase inhibitor (Anti-angiogenesis TKI) in patients with unresectable hepatocellular carcinoma (HCC).Materials and methodsOne hundred and forty-seven advanced HCC patients who received PD-1 inhibitors and TKIs as first-line systemic treatment between August 2019 and April 2021 were collected retrospectively. Fifty-four patients were finally included and divided into cTACE and no-cTACE groups, according to whether cTACE treatment was performed within 8 weeks before systemic treatment. The tumor objective response ratio (ORR), progression-free survival (PFS), overall survival (OS), and adverse events (AEs) were compared between the groups. Significant factors affecting PFS and OS were determined by Cox regression.ResultsThirty-one patients received cTACE followed by systemic treatment and 23 patients received systemic treatment only. The ORRs of the cTACE group were 48.4% (after two cycles of systemic treatment) and 51.6% (after four cycles of systemic treatment), while those of the no-cTACE group were only 17.4% and 21.7%. cTACE patients also had a longer median PFS (11.70 vs. 4.00 months, P = 0.031) and median OS (19.80 vs. 11.6 months, P = 0.006) than no-cTACE patients. Regression analyses indicated that cTACE therapy and Eastern Cooperative Oncology Group performance status were independent risk factors for PFS and OS. AEs by type were similar between the cTACE and no-cTACE groups, except for liver function injury, which was more common among cTACE patients. Fourteen patients suffered with grade 1-2 of rash in 21 patients with objective response, while only 10 patients suffered with rash in 33 patients without objective response, the adjusted hazard ratio (HR) was 4.382 (1.297–14.803).ConclusionsThe combination of cTACE and PD-1 inhibitors and anti-angiogenesis TKIs as therapy significantly improved markers of treatment efficacy, including ORR, PFS, and OS, in unresectable HCC patients, while no more serious AEs recorded in this population compared to those receiving systemic treatment alone. Skin rash might be a predict factor to the efficacy of PD-1 inhibitors and TKI treatment.

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Section: Discussionsupporting

confidence: 92%

The efficacy and safety of conventional transcatheter arterial chemoembolization combined with PD-1 inhibitor and anti-angiogenesis tyrosine kinase inhibitor treatment for patients with unresectable hepatocellular carcinoma: a real-world comparative study

Guo

Zhu²,

Zhang³

et al. 2022

Front. Oncol.

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“…A cohort of 101 HBV-HCC patients demonstrated that patients with irAEs such as rash had a much prolonged median PFS and better ORR and DCR than those without. 47 In this study, for the first time, we found that VB may be related to OS and PFS in this population. Notably, unlike the prognostic role of irAEs reported in HCC patients, 47 48 VB was an indicator of poor outcome.…”

Section: Discussionsupporting

confidence: 49%

Virological breakthrough after immune checkpoint inhibitor and nucleos(t)ide analog treatment in patients with hepatitis B surface antigen positive hepatocellular carcinoma: a real-world study

Wang

Xia

Zhu

et al. 2021

J Immunother Cancer

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BackgroundImmune checkpoint inhibitors (ICIs) have been shown to be a promising and effective treatment for hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). However, there is a lack of evidence-based data demonstrating the impact of ICIs on HBV DNA level in HBV-HCC patients undergoing nucleos(t)ide analog (NA) therapy and of HBV DNA variation on patient survival. In this study, we aimed to investigate this issue in the real world.MethodsIn this single-center retrospective study, we reviewed 182 baseline hepatitis B surface antigen (HBsAg)-positive HBV-HCC patients who were treated with ICIs and pre-emptive NAs. The demographic characteristics, tumor status, treatments, HBV DNA, HBsAg, liver function, antitumor response, and patient survival were investigated. The primary endpoints were the virological breakthrough (VB) rate, HBV reactivation (HBVr) rate, and long-term HBV DNA control; the secondary endpoints were the overall survival (OS) and progression-free survival (PFS).Results(1) VB and HBVr occurred in 18.1% (33/182) and 4.4% (8/182) of patients with a median occurrence time of 3.9 months (range, 0.7–16.0) and 8.0 months (range, 3.0–16.0), respectively. The HBV DNA negative rates were 26.1% and 0 at 24 and 48 weeks in the VB group and 12.5% and 0 in the HBVr group, respectively. A baseline HBsAg level ≥200 IU/mL was the only risk factor for VB (OR 9.9, 95% CI 2.2 to 45.2, p=0.003); (2) patients with VB had much shorter median OS and median PFS than those without (12.3 months vs 18.1 months, p=0.035; 4.5 months vs 7.5 months, p=0.011).ConclusionsThere was a high risk of VB and a moderate risk of HBVr in HBsAg-positive HBV-HCC patients (with poor long-term HBV DNA control) undergoing ICI and pre-emptive NA therapies. The only risk factor for VB was the pretreatment HBsAg level. Further, VB might be considered as a clinical biomarker predicting inferior OS and PFS in the patients.

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“…Although the mechanism underlying the occurrence of irAEs is not clear, irAEs have been shown to improve the efficacy of anti-PD-1 antibodies. The occurrence of irAEs has also been reported in liver cancer, especially in patients with rashes and with a significantly longer median PFS ( 24 ). In obese patients, the rate of inflammatory response increases and the probability of irAEs also increases ( 25 , 26 ).…”

Section: Discussion/conclusionmentioning

confidence: 93%

Body mass index, as a novel predictor of hepatocellular carcinoma patients treated with Anti-PD-1 immunotherapy

Chen

et al. 2022

Front. Med.

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Immunocheckpoint inhibitors have shown significant efficacy in the treatment of hepatocellular carcinoma (HCC), but there are individual differences. The aim of this study was to explore body mass index (BMI) as a predictor of anti-PD-1 efficacy in patients with HCC. We retrospectively analyzed 101 HCC patients who treated with anti-PD-1 at Sun Yat-sen University Cancer Center from July 2018 to November 2019 and divided them into overweight (BMI > 24.9) and non-overweight (BMI ≤ 24.9) groups based on baseline BMI levels. BMI > 24.9 accounted for 22 cases (21.8%) and BMI ≤ 24.9 accounted for 79 cases (78.2%) in the study cohort. Overweight patients had higher disease control rates than non-overweight patients (P = 0.019, respectively). The mean progression-free survival (PFS) in overweight patients (10.23 months) was significantly longer than that of non-overweight patients (6.85 months; P = 0.027). Among patients with immune-related adverse events (irAEs), the mean PFS was also significantly longer in overweight patients (7.72 months) than in non-overweight patients (5.31 months, P = 0.034). Multivariate analysis showed that BMI was an independent prognostic factor for PFS in HCC patients treated with anti-PD-1 (hazard ratio: 0.47, P = 0.044). Thus, higher BMI predicts a better prognosis among HCC patients treated with anti-PD-1. In clinical practice, patients' BMI can provide a useful tool for predicting the efficacy of anti-PD-1 therapy.

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Immune‐related adverse events predict responses to PD‐1 blockade immunotherapy in hepatocellular carcinoma

Cited by 18 publications

References 29 publications

The efficacy and safety of conventional transcatheter arterial chemoembolization combined with PD-1 inhibitor and anti-angiogenesis tyrosine kinase inhibitor treatment for patients with unresectable hepatocellular carcinoma: a real-world comparative study

The efficacy and safety of conventional transcatheter arterial chemoembolization combined with PD-1 inhibitor and anti-angiogenesis tyrosine kinase inhibitor treatment for patients with unresectable hepatocellular carcinoma: a real-world comparative study

Virological breakthrough after immune checkpoint inhibitor and nucleos(t)ide analog treatment in patients with hepatitis B surface antigen positive hepatocellular carcinoma: a real-world study

Body mass index, as a novel predictor of hepatocellular carcinoma patients treated with Anti-PD-1 immunotherapy

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