scholarly journals Immune Checkpoint Inhibitors in Oral Cavity Squamous Cell Carcinoma and Oral Potentially Malignant Disorders: A Systematic Review

Cancers ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1937 ◽  
Author(s):  
Omar Kujan ◽  
Bede van Schaijik ◽  
Camile S. Farah
Keyword(s):  
Systematic Review ◽  
Squamous Cell Carcinoma ◽  
Oral Cavity ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Survival Rates ◽  
Oral Potentially Malignant Disorders ◽  
Potentially Malignant Disorders ◽  
Potentially Malignant

Cancers of the oral cavity cause significant cancer-related death worldwide. While survival rates have improved in recent years, new methods of treatment are being investigated to limit disease progression and to improve outcomes, particularly in oral cavity squamous cell carcinoma (OSCC) and oral potentially malignant disorders (OPMD). The emerging treatment modality of immunotherapy targets immune checkpoint molecules including PD-1 and its ligand PD-L1, CTLA-4, LAG-3, and TIM-3 to enhance the host immune response against tumours, and to limit the growth and progression of cancer cells. In this systematic review, we searched five databases for keywords pertaining to oral cancers and OPMDs, along with immune checkpoint inhibitors, in order to summarize the current status of their use and efficacy in these diseases. A total of 644 different articles were identified between 2004 and 2019, with 76 deemed suitable for inclusion in the study, providing a total of 8826 samples. Combined results show expression of PD-1 and PD-L1 in the majority of OPMD and OSCC samples, with expression correlating with increased progression and decreased survival rates. Immunotherapy agents pembrolizumab and nivolumab target PD-1 and have been shown to prolong survival rates and improve disease outcomes, especially in combination with chemotherapy or radiotherapy. Despite the equivocal nature of current evidence, there is support for the prognostic and predictive value of immune checkpoint molecules, especially PD-L1, and many studies provide support for the effective use of immune checkpoint inhibitors in the management of OSCC. Limited data is available for OPMD, therefore this should be the focus of future research.

scholarly journals Neoadjuvant immunotherapy in resectable head and neck cancer: oral cavity carcinoma as a potential research model

2021 ◽  
Vol 13 ◽  
pp. 175883592098406
Author(s):  
Vanesa Gutiérrez Calderón ◽  
Alexandra Cantero González ◽  
Laura Gálvez Carvajal ◽  
Yolanda Aguilar Lizarralde ◽  
Antonio Rueda Domínguez
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Cavity ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Surgical Resection ◽  
Squamous Cell ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Research Model

Squamous cell carcinoma of oral cavity (OCSCC) accounts for approximately 25% of cases of head and neck squamous cell carcinoma (HNSCC). Tobacco and alcohol consumption are the main risk factors for both cancers. Surgical resection, combined with adjuvant radiotherapy or radiochemotherapy in patients with high risk of relapse, is the key element in management in the initial stages. However, despite the availability of aggressive multidisciplinary treatments, advanced resectable OCSCC carries poor prognosis; only half of the patients are disease-free 5 years after the surgery. Immunotherapy based on the use of immune checkpoint inhibitors has been proven to be effective in a wide variety of tumours, including recurrent and metastatic HNSCC. These positive results resulted in investigations into its effectiveness in earlier stages of the disease with OCSCC emerging as an interesting research model because of the accessible location of the tumours. This article reviews the potential advantages of emerging immunotherapeutic agents [mainly monoclonal antibodies against programmed cell death-1 ( PD-1) immune checkpoint inhibitors] as neoadjuvant treatment for OCSCC at locoregional stages as well as the ongoing clinical trials, challenges in evaluating tumour response, and possible predictive biomarkers of response with highlights regarding the role of oral microbiota as modulators of immune response. The efficacy and safety of anti- PD-1 drugs in these patients have been proven in preliminary trials. If there is a decrease in the relapse rate and an improvement in the overall survival after surgical resection in ongoing trials, preoperative immunotherapy may be established as a treatment option for patients with early stages of the disease.

scholarly journals Ipilimumab and nivolumab/pembrolizumab in advanced hepatocellular carcinoma refractory to prior immune checkpoint inhibitors

2021 ◽  
Vol 9 (2) ◽  
pp. e001945 ◽  
Author(s):  
Jeffrey Sum Lung Wong ◽  
Gerry Gin Wai Kwok ◽  
Vikki Tang ◽  
Bryan Cho Wing Li ◽  
Roland Leung ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Objective Response ◽  
Acquired Resistance ◽  
Survival Rates ◽  
Advanced Hepatocellular Carcinoma ◽  
Primary Resistance ◽  
Advanced Hcc

BackgroundProgrammed cell death protein 1 (PD-1) pathway blockade with immune checkpoint inhibitors (ICIs) is a standard therapy in advanced hepatocellular carcinoma (HCC) nowadays. No strategies to overcome ICI resistance have been described. We aimed to evaluate the use of ipilimumab and anti-PD-1 ICIs (nivolumab or pembrolizumab) combinations in patients with advanced HCC with progression on prior ICIs.MethodsPatients with advanced HCC with documented tumor progression on prior ICIs and subsequently received ipilimumab with nivolumab/pembrolizumab were analyzed. Objective response rate (ORR), median duration of response (DOR), time-to-progression (TTP), overall survival (OS), and treatment-related adverse events (TRAEs) were assessed.ResultsTwenty-five patients were included. The median age was 62 (range: 51–83). About 68% were of Child-Pugh (CP) Grade A and 48% had primary resistance to prior ICI. At median follow-up of 37.7 months, the ORR was 16% with a median DOR of 11.5 months (range: 2.76–30.3). Three patients achieved complete response. The median TTP was 2.96 months (95% CI: 1.61 to 4.31). Median OS was 10.9 months (95% CI: 3.99 to 17.8) and the 1 year, 2 year and 3 year survival rates were 42.4%, 32.3% and 21.6%, respectively. The ORR was 16.7% in primary resistance group and 15.4% in acquired resistance group (p=1.00). All responders were of CP A and Albumin-Bilirubin (ALBI) Grade 1 or 2. CP and ALBI Grades were significantly associated with OS (p=0.006 and p<0.001, respectively). Overall, 52% of patients experienced TRAEs and 12% experienced Grade 3 or above TRAEs.ConclusionsIpilimumab and nivolumab/pembrolizumab can achieve durable antitumor activity and encouraging survival outcomes with acceptable toxicity in patients with advanced HCC who had prior treatment with ICIs.

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