Correlation Between Immune-Related Adverse Events and Prognosis in Hepatocellular Carcinoma Patients Treated With Immune Checkpoint Inhibitors.

Immune-related adverse events (irAEs) caused by immune checkpoint inhibitors (ICIs) were associated with clinical benefit in cancer patients of melanoma, a lung cancer. In the present study, we investigated the correlation between irAE and ICI efficacy in hepatocellular carcinoma (HCC) patients. We divided the HCC patients who received the anti-PD-1 antibody into two groups as irAE group and non-irAE group according to the National Cancer Institute Common Terminology Criteria for Adverse Events ver. 4.03. The treatment efficacy of ICIs was evaluated with objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). Of the 65 HCC patients who received the anti-PD-1 antibody (monotherapy or combined with targeted medicine), median PFS in the irAE group was superior to that in the non-irAE group (302 days vs. 148 days, p = 0.004). Median OS in the irAE group was also better than that in the non-irAE group (374 days vs. 279 days, p = 0.038). Although the statistical difference for DCR in the irAE group and non-irAE group was not reached, the DCR of the irAE displayed a trend better than that of the non-irAE group (41.20% vs. 20.80%, p = 0.118). Multivariate analysis also demonstrated that the non-irAE group (HR = 6.410, 95% CI: 1.404 to 29.275) was associated independently with the poor prognosis. Development of irAEs was associated with clinical benefit for HCC patients who were treated with immune checkpoint inhibitors; irAE, particularly low-grade irAE, was a predictable marker for better ICI treatment efficiency in HCC patients.

Xu S ，Lai R ，Zhao Q ，Zhao P ，Zhao R ，Guo Z ... -  《Frontiers in Immunology》

Are anti-PD-1-associated immune related adverse events a harbinger of favorable clinical prognosis in patients with gastric cancer?

Immune checkpoint inhibitors (ICIs) has shown remarkable benefit in the treatment of a range of cancer types, although it may initiate immune related adverse events (irAEs) in patients. Some studies have shown that there is a close relationship between the occurrence of irAEs and prognosis. In present study, we have attempted to establish whether the occurrence of irAEs after the use of anti PD-1 antibodies is associated with treatment efficacy in people with advanced gastric cancer (AGC). This study included patients treated with the anti-PD-1 antibodies for AGC patients at The Fourth Hospital of Hebei Medical University. IrAEs were identified clinically and graded as per the National Cancer Institute Common Terminology Criteria for Adverse Events ver. 4.03. Efficacy was evaluated with objective response rate (ORR), disease control rate (DCR), progression free survival (PFS) and overall survival (OS). The analysis was performed to determine the association between irAEs and clinical outcomes. Of the 74 AGC patients in our study, 24 developed irAEs. The DCR of the irAE displayed a trend better than that of non-irAE group but without statistical difference (41.70% VS 6.0%, p = 0.118). Median PFS in the irAE group was superior to that in the non-irAE group (176 days VS 94 days, p = 0.001). Median OS also showed this trend of difference at borderline statistical level (292 days VS 239 days, p = 0.057). Multivariate analysis also demonstrated irAE (HR = 0.269, 95%CI: 0.088 to 0.822, p = 0.021) were associated independently with the better prognosis for AGC patients. In advanced gastric cancer treated with anti PD-1 antibodies, the occourence of irAEs might contribute to the improved prognosis.

Zhang X ，Xu S ，Wang J ，Lv Y ，Wang N ，Lai R ，Sha Z ，Zhao Q ，Guo Z ... -  《-》

Impact of immune-related adverse events in patients with hepatocellular carcinoma treated with atezolizumab plus bevacizumab.

Immune checkpoint inhibitors pose the risk of immune-related adverse events (irAEs). Recent data suggest that irAEs may be associated with a favorable prognosis. This study aimed to investigate and analyze the association between these adverse events and the clinical benefits in patients with unresectable hepatocellular carcinoma. The study enrolled 130 patients with advanced hepatocellular carcinoma treated with atezolizumab plus bevacizumab between November 2020 and January 2023 at a single center. The relationship between irAEs and both response rate and post-treatment outcomes was investigated. Out of the 130 patients, irAEs developed in 36 (27.7%) patients. The irAE group exhibited a significantly longer progression-free survival (PFS) than the non-irAE group, with a median PFS of 8.9 compared with 4.6 months (P < 0.01). No difference was found in the overall survival between the irAE and non-irAE groups. The irAE group demonstrated significantly higher disease control rate (DCR) than the non-irAE group (97.0% vs 65.5%, P < 0.01). The analysis by irAE severity revealed that the grade 1/2 group exhibited significantly longer PFS (7.9 vs 4.6 months, P = 0.007) and higher DCR (100% vs 65.5%, P < 0.01) than the non-irAE group. Furthermore, hypothyroidism correlated with a favorable PFS (8.9 vs 5.4 months, P = 0.02), DCR (100% vs 71.3%, P = 0.03), and overall response rate (58.3% vs 18.5%, P = 0.005). The presence of irAEs is associated with prolonged PFS and higher DCR. Specifically, mild irAEs (grade 1/2) and hypothyroidism displayed prolonged PFS and higher DCR.

Suzuki K ，Yasui Y ，Tsuchiya K ，Matsumoto H ，Yamazaki Y ，Uchihara N ，Tanaka Y ，Miyamoto H ，Yamada-Shimizu M ，Keitoku T ，Okada R ，Higuchi M ，Takaura K ，Tanaka S ，Maeyashiki C ，Tamaki N ，Nakanishi H ，Takahashi Y ，Asahina Y ，Okamoto R ，Kurosaki M ，Izumi N ... -  《-》

Correlation between immune-related adverse events and prognosis in patients with gastric cancer treated with nivolumab.

Masuda K ，Shoji H ，Nagashima K ，Yamamoto S ，Ishikawa M ，Imazeki H ，Aoki M ，Miyamoto T ，Hirano H ，Honma Y ，Iwasa S ，Okita N ，Takashima A ，Kato K ，Boku N ... -  《BMC CANCER》

Association between immune-related adverse events and the efficacy of PD-1 inhibitors in advanced esophageal cancer.

Recent developments in immune checkpoint inhibitors (ICIs) have improved the treatment outcomes of esophageal cancer (EC); however, it may initiate immune-related adverse events (irAEs) in some patients. The ICIs' therapeutic efficacy is associated with irAEs in patients with non-small cell lung cancer or renal cell carcinoma, although this association is unknown in EC. The purpose of this study was to explore the association between irAEs and the efficacy of programmed death 1 (PD-1) inhibitors in EC patients. This study included patients with advanced EC treated with PD-1 inhibitors. The patients were divided into two groups according to the occurrence of irAEs. Afterward, the efficacy was compared between the irAE-negative and irAE-positive groups, and we analyzed the predictive factors of irAEs and survival. Overall, 295 patients were included in this study. Baseline characteristics were balanced in the irAE-negative and irAE-positive groups. In total, 143 (48.47%) patients experienced irAEs. The most frequent irAEs were anemia (49, 16.61%), hyperthyroidism (45, 15.25%), and pneumonitis (44, 14.92%). In total, 33 (11.19%) patients had grade ≥ 3 irAEs and pneumonitis have 15 (5.08%). No grade 5 adverse events were observed. A total of 52 (17.63%) and 91 (30.85%) patients had single and multiple irAEs, respectively. Compared with patients without irAEs, those with irAEs had significantly higher objective response rate (ORR) (37.76% vs. 25.00%, p = 0.018) and disease control rate (DCR) (92.31% vs. 83.55%, p = 0.022). Univariate Cox analyses indicated the significant association between irAEs and improved median progression-free survival (PFS) (10.27 vs. 6.2 months, p < 0.001) and overall survival (OS) (15.4 vs. 9.2 months, p < 0.001). In multivariate analyses, irAEs were independently associated with longer PFS (p = 0.011) and OS (p = 0.002). Moreover, multivariate analysis revealed that cycles > 8, radiation, as well as antiangiogenic therapy were strongly associated with irAEs development (p < 0.001, p = 0.002, and p = 0.025, respectively). In advanced EC, patients with irAEs showed markedly better efficacy in ORR, DCR, PFS, and OS compared with patients without irAEs.

Qin W ，Yang L ，Fan B ，Zou B ，Duan Y ，Li B ，Wang L ... -  《Frontiers in Immunology》