Toxicity profiles of immune checkpoint inhibitors for recurrent or metastatic head and neck squamous cell carcinoma: A systematic review and meta‐analysis
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ABSTRACT:
SUBMITTER: Dang S
PROVIDER: S-EPMC10980932 | biostudies-literature | 2024 Mar
REPOSITORIES: biostudies-literature
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Project description:BackgroundReduced muscle mass has been associated with increased treatment complications in several tumor types. We evaluated the impact of skeletal muscle index (SMI) on prognosis and immune-related adverse events (IrAEs) in a cohort of recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) treated with immune checkpoints inhibitors (ICI).MethodsA single-institutional, retrospective study was performed including 61 consecutive patients of R/M HNSCC diagnosed between July 2015 and December 2018. SMI was quantified using a CT scan at L3 to evaluate body composition. Median baseline SMI was used to dichotomize patients in low and high SMI. Kaplan-Meier estimations were used to detect overall survival (OS) and progression-free survival (PFS). Toxicity was recorded using Common Terminology Criteria for Adverse Event v4.3.ResultsPatients were 52 men (85.2%) with mean of age 57.7 years (SD 9.62), mainly oral cavity (n = 21; 34.4%). Low SMI was an independent factor for OS in the univariate (HR, 2.06; 95% CI, 1.14-3.73, p = 0.017) and multivariate Cox analyses (HR, 2.99; 95% CI, 1.29-6.94; p = 0.011). PFS was also reduced in patients with low SMI (PFS HR, 1.84; 95% CI, 1.08-3.12; p = 0.025). IrAEs occurred in 29 (47.5%) patients. There was no association between low SMI and IrAEs at any grade (OR, 0.56; 95% CI, 0.20-1.54; p = 0.261). However, grades 3 to 4 IrAEs were developed in seven patients of whom three had low SMI.ConclusionsLow SMI before ICI treatment in R/M HNSCC patients had a negative impact on OS and PFS. Further prospective research is needed to confirm the role of body composition as a predictive biomarker in ICI treatment.
| S-EPMC8267860 | biostudies-literature
Project description:Aim: This study addresses the challenge of predicting the response of head and neck squamous cell carcinoma (HNSCC) patients to immunotherapy.Methods: Using DNA methylation cytometry, we analyzed the immune profiles of six HNSCC patients who showed a positive response to immunotherapy over a year without disease progression.Results: There was an initial increase in CD8 T memory cells and natural killer cells during the first four cycles of immunotherapy, which then returned to baseline levels after a year. Baseline CD8 T cell levels were lower in HNSCC immunotherapy responders but became similar to those in healthy subjects after immunotherapy.Conclusion: These findings suggest that monitoring fluctuations in immune profiles could potentially identify biomarkers for immunotherapy response in HNSCC patients.
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Project description:Preclinical data suggest that head and neck squamous cell carcinomas (HNSCC) may evade immune surveillance and induce immunosuppression. One mechanism of immune evasion involves the expression of programmed death ligand-1 (PD-L1) in tumor and immune cells, which is, to date, the only biomarker routinely used in clinical practice to select patients with advanced HNSCCs more likely to benefit from anti-PD-1 therapy. Nonetheless, PD-L1 expression alone incompletely captures the degree of sensitivity of HNSCCs to PD-1 inhibitors. Most patients exposed to anti-PD-1 antibodies do not respond to therapy, suggesting the existence of mechanisms of de novo resistance to immunotherapy. Furthermore, patients that initially respond to PD-1 inhibitors will eventually develop acquired resistance to immunotherapy through mechanisms that have not yet been completely elucidated. In this article, we will provide an overview of the immune landscape of HNSCCs. We will briefly describe the clinical activity of inhibitors of the PD-1/PD-L1 axis in this disease, as well as biomarkers of benefit from these agents that have been identified so far. We will review pre-clinical and clinical work in cancers in general, and in HNSCCs specifically, that have characterized the mechanisms of de novo and acquired resistance to immunotherapy. Lastly, we will provide insights into novel strategies under investigation to overcome resistance to immune checkpoint inhibitors.
| S-EPMC7973277 | biostudies-literature
Project description:Anti-programmed cell death protein 1 (PD-1) agents have become the standard of care for platinum-refractory recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) and are currently being evaluated in various disease settings. However, despite the gain in overall survival seen in some of the clinical trials, the majority of patients display primary resistance and do not benefit from these agents. Taking into consideration the potentially severe immune-related toxicities and their high cost, the search for predictive biomarkers of response is crucial. Besides Programmed death ligand-1 (PD-L1) expression, other biomarkers such as immune infiltration, tumor mutational burden or immune-gene expression profiling have been explored, but none of them has been validated in this disease. Among these, the microbiota has recently garnered tremendous interest since it has proven to influence the efficacy of PD-1 blockade in some tumor types. With the accumulating evidence on the effect of the microbiota in HNSCC tumorigenesis and progression, the study of its potential role as a predictive immune biomarker is warranted. This review examines the available evidence on emerging immune predictive biomarkers of response to anti-PD-1/PD-L1 therapy in HNSCC, introducing the microbiota and its potential use as a predictive immune biomarker in this disease.
| S-EPMC6336003 | biostudies-literature
Project description:BackgroundImmune checkpoint inhibitors (ICIs) showed antitumor activity for recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC). However, the results from different studies were controversial.MethodsOnline databases were searched for randomized clinical trials (RCTs) evaluating ICIs for R/M HNSCC. The characteristics of the studies and the results of overall survival (OS), progression-free survival (PFS), objective response rate (ORR), treatment-related adverse events (TRAEs) were extracted.ResultsA total of 4936 patients from eight studies were included. Anti-PD1/PDL1 monotherapy significantly improved OS in total population (hazard ratio, HR, 0.87, 95% CI, 0.79-0.95, p = 0.003) and PD-L1 high expression patients (HR, 0.71, 95% CI, 0.55-0.90, p = 0.006) with significant lower incidence of any grade TRAEs (odds ratio, OR, 0.16, 95% CI, 0.07-0.37, p < 0.00001) and Grades 3-5 TRAEs (OR, 0.18, 95% CI, 0.10-0.33, p < 0.0001) compared with standard of care (SOC); however, the pooled results of PFS and ORR were not significant different. PD1/PDL1 inhibitors plus CTLA4 inhibitors did not improve OS, PFS, ORR compared with SOC or ICIs monotherapy; however, the incidence of Grades 3-5 TRAEs was significant higher compared with ICIs monotherapy (OR, 1.80, 95% CI, 1.34-2.41, p = 0.0001).ConclusionsAnti-PD1/PDL1 monotherapy could improve OS for R/M HNSCC with significant lower incidence of TRAEs compared with SOC. PD1/PDL1 inhibitors plus CTLA4 inhibitors showed no more benefit compared with both SOC and ICIs monotherapy, but the incidence of Grades 3-5 TRAEs was significant higher compared with ICIs monotherapy.
| S-EPMC10652313 | biostudies-literature
Project description:New diagnostic methods and novel therapeutic agents spawn additional and heterogeneous information, leading to an increasingly complex decision-making process for optimal treatment of cancer. A great amount of information is collected in organ-specific multidisciplinary tumor boards (MDTBs). By considering the patient's tumor properties, molecular pathological test results, and comorbidities, the MDTB has to consent an evidence-based treatment decision. Immunotherapies are increasingly important in today's cancer treatment, resulting in detailed information that influences the decision-making process. Clinical decision support systems can facilitate a better understanding via processing of multiple datasets of oncological cases and molecular genetic information, potentially fostering transparency and comprehensibility of available information, eventually leading to an optimum treatment decision for the individual patient. We constructed a digital patient model based on Bayesian networks to combine the relevant patient-specific and molecular data with depended probabilities derived from pertinent studies and clinical guidelines to calculate treatment decisions in head and neck squamous cell carcinoma (HNSCC). In a validation analysis, the model can provide guidance within the growing subject of immunotherapy in HNSCC and, based on its ability to calculate reliable probabilities, facilitates estimation of suitable therapy options. We compared actual treatment decisions of 25 patients with the calculated recommendations of our model and found significant concordance (Cohen's κ = 0.505, p = 0.009) and 84% accuracy.
| S-EPMC8657168 | biostudies-literature
Project description:Little is known about changes in the abundance of tumor-infiltrating lymphocytes (TILs) and immune phenotype (IP) in recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). We aimed to compare the TILs and IP between initial and recurrent HNSCCs using paired analysis. Thirty-seven patients who experienced recurrence after surgical resection and received treatment with immune checkpoint inhibitors (ICIs) between June 2014 and June 2023 were included. Changes in intratumoral TIL (iTILs), stromal TIL (sTILs), and IPs were subjected to paired analysis between the initial and recurrent tumors. We investigated their relationship with the outcomes of ICIs. The density of iTIL and sTIL in the recurrent tumors was significantly lower compared to initial tumors. IP was significantly different; the proportion of desert IP was higher in recurrent tumors (83.8% vs. 35.1%, P < 0.001). Increased sTIL was a favorable indicator for overall response to ICIs and progression-free survival. Our findings suggest TILs decrease during recurrence compared with the initial tumor, resulting in a transition toward desert IP. Therefore, careful evaluation of TIL density in both initial and recurrent tumors is recommended when using ICIs in patients with R/M HNSCC.
| S-EPMC11579274 | biostudies-literature
Project description:This study aimed to determine the prognostic value of inflammatory and nutritional biomarkers of immune checkpoint inhibitor (ICI) therapy for recurrent or metastatic squamous cell carcinoma of the head and neck (RMHNSCC) and to identify the most useful factor for prognosis assessment. We retrospectively reviewed the medical records of patients with RMHNSCC who received ICI therapy. The response rate for ICI therapy and the relationship between inflammatory and nutritional biomarkers and overall survival were examined. The included biomarkers did not correlate with an objective response rate but were associated with a disease control rate. Univariate analysis showed significant correlations between the serum albumin level, C-reactive protein level, platelet to lymphocyte ratio, neutrophil to lymphocyte ratio, lymphocyte to monocyte ratio (LMR), systemic immune-inflammation index, and controlling the nutritional status score and overall survival; multivariate analysis showed that LMR was significantly correlated with overall survival. LMR was the most important biomarker according to the machine learning model. This study suggests that LMR may be the most useful biomarker for predicting the prognosis of ICI treatment for RMHNSCC.
| S-EPMC10093403 | biostudies-literature
Project description:BackgroundImmune checkpoint inhibitors (ICIs) are essential in treating recurrent/metastatic squamous cell carcinoma of the head and neck (R/M SCCHN). However, the overall response rate (ORR) is limited to 10-20%, and subsequent chemotherapy is critical to maximizing the subjects' prognosis.MethodsWe retrospectively reviewed 59 patients with R/M SCCHN treated with paclitaxel+cetuximab (PE)-based chemotherapy (PCE, paclitaxel+carboplatin+cetuximab; or PTX+Cmab, paclitaxel+cetuximab) following disease progression after either pembrolizumab or nivolumab monotherapy.ResultsOf 59 patients, 15 were treated with pembrolizumab, with an ORR of 13.3%, and the remaining 44 with nivolumab, with an ORR of 11.4%. All patients in the pembrolizumab cohort had platinum-sensitive disease. Following ICI treatment, 19 patients were treated with PCE and the remaining 40 with PTX+Cmab. PE-based chemotherapy induced favorable and prompt tumor shrinkage even in cases where ICI was not effective, with a median change in the summed dimensions of target lesions of -43.4%, resulting in an ORR of 62.7%. Median time to response was 1.8 months. The patients in the pembrolizumab cohort appeared to have a numerically higher response rate than those receiving nivolumab (80.0% vs. 56.8%). For the 59 patients, progression-free survival and overall survival, calculated from the initiation of PE-based chemotherapy, were 4.6 months and 17.1 months, respectively. Grade ≥3 adverse events occurred in 40.7%, and no treatment-related death was observed.ConclusionPE-based chemotherapy following ICI is encouraging for its robust antitumor efficacy in R/M SCCHN.
| S-EPMC10703151 | biostudies-literature
Project description:ObjectivesThe benefit of sequential therapy after immune checkpoint inhibitor (ICI) treatment for recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) has been recently reported. Furthermore, there is a growing interest in the impact of cetuximab (Cmab)-containing salvage chemotherapy (SCT) and the therapeutic efficacy and adverse events (AEs) of Cmab administration prior to ICI administration.Materials and methodsWe retrospectively reviewed the medical records of 52 patients with R/M HNSCC treated with SCT (weekly paclitaxel [PTX], n = 7, or weekly PTX and Cmab [PC], n = 45).ResultsThe objective response rate (ORR) and a disease control rate (DCR) was 53.3% and 91.1% in the PC group and 42.9% and 57.1% in the PTX group, respectively. There was a significant difference in the DCR between the PC and PTX groups (p = 0.0143). The overall survival (OS) and progression-free survival were significantly better in the PC group than in the PTX group. On the other hand, the incidence of drug-induced interstitial pneumonia (DI-IP) in R/M HNSCC patients who received SCT was 21.2%. Patients in the PC group were divided according to whether they received Cmab (Group A) or did not receive Cmab (Group B) as palliative therapy prior to ICIs. Group B had a significantly better OS than Group A. Furthermore, our findings suggest that the incidence rate of DI-IP during SCT might be higher in Group B.ConclusionAlthough PC following ICIs shows dramatic efficacy, careful monitoring of AEs, including DI-IP, is recommended.
| S-EPMC9333293 | biostudies-literature