Immune-related ocular toxicities in solid tumor patients treated with immune checkpoint inhibitors: a systematic review

Abstract Background Most immune-related adverse event (irAE) patterns and treatment guidelines are based on western clinical data. We evaluated the incidence and patterns of irAEs in patients treated with immune-checkpoint inhibitors (ICI) in Thailand. Methods All solid tumor patients treated with ICIs were retrospectively reviewed in a multicenter analysis. The study aims to evaluate the incidence of irAEs and their characteristics, treatments, outcomes, and impact on survival. All irAEs were graded using the CTCAE version 4.0. Characteristics of irAEs including time to onset, duration of irAEs, specific treatments, and outcomes of irAEs were reviewed. The Chi-square or Fisher’s exact test was used to compare variables. Overall survival (OS) was estimated by the Kaplan-Meier method, and compared by the log-rank test. A p-value < 0.05 was considered statistically significant. Results irAEs of any grade were observed in 98 of 414 patients (24%), whereas grades 3–4 irAEs were observed in 5.6%. The majority of patients (78%) were treated with monotherapy ICI (anti-PD1/PD-L1 92%). The most common all-grade irAEs were hypothyroidism (7.5%), hepatitis (6.5%), and rash (4.8%). Median onset of overall irAEs was 63 days. Pancreatitis and pneumonitis had the earliest onset at 30 and 34 days, respectively. ICIs were rechallenged in 68 of 98 patients with irAE. Eleven of sixty-eight patients (11.2%) with initial irAE had reoccurrence after ICI rechallenge. Based on a multivariate analysis, pre-existing hypothyroidism, ICI used in a clinical trial setting, and combinations of ICI/ICI were independent factors predicting irAE occurrence. Patients with irAE had a statistically significant longer overall survival (OS) when compared to patients without irAE (p = 0.019). A multivariate analysis revealed that occurrence of irAE was an independent prognostic factor for OS (HR 0.70, 95% CI 0.51–0.96; p = 0.028). Conclusion irAE was commonly observed in Thai cancer patients treated with ICIs. Most irAEs were low-grade and manageable. Re-occurrence of irAE after re-challenging ICI was not uncommonly observed. Patients who experienced irAEs might have significantly longer OS compared to patients without irAEs. However, OS in this study should be interpreted with caution since it might be affected by various tumor types, treatment settings, dosing schedule, and ICI combinations.

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High pretreatment neutrophil-to-lymphocyte ratio (NLR) and its reactive increase as better predictors of poor clinical outcomes compared to tumor mutation burden (TMB) in solid tumor patients treated with immune checkpoint inhibitors (ICI).

Journal of Clinical Oncology ◽

10.1200/jco.2018.36.15_suppl.e24109 ◽

2018 ◽

Vol 36 (15_suppl) ◽

pp. e24109-e24109

Author(s):

Vaia Florou ◽

Wungki Park ◽

Alfredo Enrique Torres ◽

Sandra Algaze ◽

Diana Saravia ◽

...

Keyword(s):

Clinical Outcomes ◽

Solid Tumor ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Neutrophil To Lymphocyte Ratio ◽

Tumor Patients ◽

Tumor Mutation Burden ◽

Lymphocyte Ratio ◽

Mutation Burden

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The prevalence of homologous recombination deficiency (HRD) in various solid tumors and the role of HRD as a single biomarker to immune checkpoint inhibitors

Journal of Cancer Research and Clinical Oncology ◽

10.1007/s00432-021-03781-6 ◽

2021 ◽

Author(s):

Hana Kim ◽

Soomin Ahn ◽

Hongsik Kim ◽

Jung Yong Hong ◽

Jeeyun Lee ◽

...

Keyword(s):

Homologous Recombination ◽

Solid Tumor ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Rare Cancer ◽

Tumor Patients ◽

Homologous Recombination Deficiency ◽

Significant Difference ◽

The Status

Abstract Purpose Homologous recombination deficiency (HRD) is related to tumorigenesis. Currently, the possibility of HRD as a prognostic biomarker to immune checkpoint inhibitors is unknown. We aimed to investigate whether HRD has potential as a biomarker for immunotherapy. Methods The status of homologous recombination deficiency (HRD) was assessed with the next-generation sequencing (NGS) TruSight™ Oncology 500 assay in 501 patients with advanced solid tumor including gastrointestinal (GI), genitourinary (GU), or rare cancer. Results: among the 501 patients, HRD was observed as follows: 74.7% (347/501) patients; GU cancer (92.0%, 23 of 25), colorectal cancer (CRC) (86.1%, 130 of 151), hepatocellular carcinoma (HCC) (83.3%, 10 of 12), pancreatic cancer (PC) (76.2%, 32 of 42), biliary tract cancer (BTC) (75.0%, 36 of 48), sarcoma (65.0%, 39 of 60), melanoma (52.4%, 11 of 21), other GI cancers (50.0%, 11 of 22), and rare cancer (50.0%, 2 of 4). Sixty-five of the 501 patients had received immune checkpoint inhibitors (ICIs) during the course of the disease. Tumor types of 65 patients treated with ICIs are as follows: melanoma (95.2%, 20 of 21), HCC (33.3%, 4 of 12), rare cancer (25.0%, 1 of 4), GC (12.2%, 14 of 116), BTC (10.4%, 5 of 48), and sarcoma (5.0%, 3 of 60). The most frequently reported mutations were BRCA2 (n = 90), ARID1A (n = 77), ATM (n = 71), BARD1 (n = 67). Patients without HRD exhibited an objective response rate (ORR) of 33.3% (4 of 12), and patients with HRD exhibited an ORR of 34.0% (18 of 53). There was no significant difference in ORR between patients with and without HRD (P = 0.967). Progression-free survival (PFS) was 6.5 months (95% CI 0.000–16.175) in patients without HRD and 4.1 months (95% CI 2.062–6.138) in patients with HRD, revealing no statistical significance (P = 0.441). Conclusion Herein, we reported the status of HRD using a cancer-panel for various solid tumor patients in routine clinical practice and demonstrated that HRD as a single biomarker was not sufficient to predict efficacy of ICIs in solid tumor patients.

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