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》

Multisystem Immune-Related Adverse Events Associated With Immune Checkpoint Inhibitors for Treatment of Non-Small Cell Lung Cancer.

Shankar B ，Zhang J ，Naqash AR ，Forde PM ，Feliciano JL ，Marrone KA ，Ettinger DS ，Hann CL ，Brahmer JR ，Ricciuti B ，Owen D ，Toi Y ，Walker P ，Otterson GA ，Patel SH ，Sugawara S ，Naidoo J ... -  《-》

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 ... -  《-》

Correlation between immune-related adverse events and efficacy of PD-(L)1 inhibitors in small cell lung cancer: a multi-center retrospective study.

Patients receiving PD-(L)1 inhibitors frequently encounter unusual side effects known as immune-related adverse events (irAEs). However, the correlation of irAEs development with clinical response in small cell lung cancer (SCLC) is unknown. This retrospective study enrolled 244 stage IV SCLC patients who receiving PD-(L)1 inhibitors from 3 cancer centers. The correlation of irAEs with objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) were evaluated. 140 in 244 (57%) patients experienced irAEs, with 122 (87.1%) experiencing one and 18 (12.9%) experiencing two or more. Compared to patient without irAEs, those developing irAEs had higher ORR (73.6% vs. 52.9%, P < 0.001) and DCR (97.9% vs. 79.8%, P < 0.001), as well as prolonged median PFS (8.8 vs. 4.5 months, P < 0.001) and OS (23.2 vs. 21.6 months, P < 0.05). Among the different spectra of irAEs, thyroid dysfunction, rash, and pneumonitis were the most powerful indicator for improved PFS. When analyzed as a time-dependent covariate, the occurrence of irAEs was associated with significant improvement in PFS rather than in OS. Furthermore, patients experiencing multisystem irAEs displayed a longer PFS and OS compared with single-system irAEs and the irAE-free ones. IrAEs grade and steroid use did not impact the predictive value of irAEs on PFS. The presence of irAEs predicts superior clinical benefit in SCLC. Patients who develop multi-system irAEs may have an improved survival than those developed single-system irAEs and no-irAEs. This association persists even when systemic corticosteroids were used for irAEs management.

Zhang J ，Gao A ，Wang S ，Sun Y ，Wu J ，Wang D ，Ge Y ，Li J ，Sun H ，Cheng Q ，Sun Y ... -  《RESPIRATORY RESEARCH》

Association of Immune-Related Adverse Events and the Efficacy of Anti-PD-(L)1 Monotherapy in Non-Small Cell Lung Cancer: Adjusting for Immortal-Time Bias.

Yu Y ，Chen N ，Yu S ，Shen W ，Zhai W ，Li H ，Fan Y ... -  《-》