Immunotherapy in Head and Neck Cancer: Where Do We Stand?

Evangelopoulos, Angelos; Kounatidis, Dimitris; Panagopoulos, Fotis; Geladari, Eleni; Karampela, Ιrene; Stratigou, Theodora

doi:10.1007/s11912-023-01425-1

Cited by 14 publications

(8 citation statements)

References 102 publications

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“…It should be emphasized that both PD-1 and PD-L1 expression on immune cells are favorable prognostic biomarkers in patients with HPV-related OPSCC [ 30 , 31 ]. Recently, immune checkpoint inhibitors such as pembrolizumab and nivolumab have been approved for the treatment of patients with recurrent or metastatic disease [ 32 ].…”

Section: Discussionmentioning

confidence: 99%

Pretreatment Circulating HPV16 DNA Viral Load Predicts Risk of Distant Metastasis in Patients with HPV16-Positive Oropharyngeal Cancer

Mazurek,

Jabłońska,

Kentnowski

et al. 2024

Cancers

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Background: There are definite reasons to implement molecular diagnostics based on the measurement of human papillomavirus (HPV) DNA in liquid biopsy into clinical practice. It is a quick, repeatable, and health-safe test for cancer biomarkers in the blood. In this study, we investigated whether the circulating tumor-related HPV16 (ctHPV16) viral load (VL) in patients with oropharyngeal squamous cell carcinoma (OPSCC) was important for determining the risk of locoregional recurrence-free survival (LRFS), metastasis-free survival (MFS), and overall survival (OS). Methods: This study included 91 patients with ctHPV16-positive OPSCC who had been treated with radical radiotherapy and chemotherapy. The VL was measured using quantitative PCR (qPCR) and a probe specific for HPV16. Based on 10 years of follow-up, the 2-, 3-, 5-, and 9-year LRFS, MFS, and OS were estimated. Results: The 5-year actuarial LRFS, MFS, and OS rates of patients with ctHPV16-positive/OPSCC were 88%, 90%, and 81%, respectively. The VL was significantly higher in patients who subsequently developed distant metastases (DM) than in those who did not (VL 4.09 vs. 3.25; p = 0.009). In a Cox proportional hazards regression model for MFS, a higher ctHPV16 VL appeared to be a significant independent prognostic factor for the occurrence of DM (HR 2.22, p = 0.015). The ROC curve revealed a cutoff value of 3.556 for VL (p = 0.00001). Conclusions: A high VL before treatment indicates patients with a significant risk of DM, and should be used in OPSCC treatment stratification.

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Section: Discussionmentioning

confidence: 99%

Pretreatment Circulating HPV16 DNA Viral Load Predicts Risk of Distant Metastasis in Patients with HPV16-Positive Oropharyngeal Cancer

Mazurek,

Jabłońska,

Kentnowski

et al. 2024

Cancers

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“…FDA approved immunotherapies for HNSCC have centered around manipulating the PD1/PD-L1 axis [ 43 , 44 ] and historically have been limited to the setting of metastatic and recurrent disease [ 45 , 46 ]. Clinical trials to date using immunotherapy for locally advanced HNSCC have either demonstrated no significant improvement in overall survival (NCT02952586) or are still in early phases [ 14 , 16 ].…”

Section: Discussionmentioning

confidence: 99%

IL7 in combination with radiotherapy stimulates a memory T-cell response to improve outcomes in HNSCC models

Yu,

Gadwa,

Ross

et al. 2024

Cancer Immunol Immunother

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Clinically approved head and neck squamous cell carcinoma (HNSCC) immunotherapies manipulate the immune checkpoint blockade (ICB) axis but have had limited success outside of recurrent/metastatic disease. Interleukin-7 (IL7) has been shown to be essential for effector T-cell survival, activation, and proliferation. Here, we show that IL7 in combination with radiotherapy (RT) is effective in activating CD8 + T-cells for reducing tumor growth. Our studies were conducted using both human papillomavirus related and unrelated orthotopic HNSCC murine models. Immune populations from the tumor, draining lymph nodes, and blood were compared between treatment groups and controls using flow cytometry, proteomics, immunofluorescence staining, and RNA sequencing. Treatment with RT and IL7 (RT + IL7) resulted in significant tumor growth reduction, high CD8 T-cell tumor infiltration, and increased proliferation of T-cell progenitors in the bone marrow. IL7 also expanded a memory-like subpopulation of CD8 T-cells. These results indicate that IL7 in combination with RT can serve as an effective immunotherapy strategy outside of the conventional ICB axis to drive the antitumor activity of CD8 T-cells.

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“…In the future, we anticipate an expansion randomized clinical trials with larger sample sizes and multi-center involvement, thereby facilitating more precise patient stratification. Additionally, the combination of immunotherapeutic agents with other modalities remains an area of significant interest ( 53 ). For patients with metastatic non-small cell carcinoma lung cancer (mNSCLC), the addition of durvalumab and four cycles of chemotherapy to a single course of tremelimumab demonstrates long-term survival benefits, early disease control, and manageable tolerability without compromising treatment exposure ( 54 ).…”

Section: Discussionmentioning

confidence: 99%

Durvalumab with or without tremelimumab for patients with recurrent or metastatic squamous cell carcinoma of the head and neck: a systematic review and meta-analysis

Han,

Zhang,

Sun

et al. 2024

Front. Immunol.

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ObjectiveHead and neck squamous cell carcinoma (HNSCC) ranks as the sixth most prevalent cancer worldwide, significantly impacting patients’ quality of life. Immune checkpoint inhibitors (ICI) have been employed in the treatment of recurrent/metastatic (R/M)-HNSCC patients. This meta-analysis aims to assess the efficacy and safety of durvalumab monotherapy compared to the combination of durvalumab and tremelimumab in R/M-HNSCC patients.MethodsRelevant studies were systematically searched in PubMed, Embase, and Cochrane Library databases. All articles comparing durvalumab monotherapy with the combination with durvalumab and tremelimumab in R/M-HNSCC treatment were included. Additionally, the references of identified studies were screened if necessary.ResultA total of 1298 patients from three studies comparing durvalumab with durvalumab and tremelimumab in treating R/M-HNSCC were include in this meta-analysis. Our findings revealed no significant difference in objective response rate (ORR) [odds ratio (OR): 1.15, 95% confidence interval (CI): 0.85 to 1.56, P = 0.36] and disease control rate (DCR) (OR=1.08, 95%CI: 0.86 to 1.37, P = 0.51). Similar outcomes were observed in overall survival (OS), progression-free survival (PFS), and duration of response (DoR). Regarding safety, there was no significant difference in the incidence of treatment-related adverse events (trAEs) between the two groups (OR=1.26, 95%CI: 0.81 to 1.94, P = 0.30). However, patients treated with the combination therapy exhibited a higher incidence of grade 3-4 trAEs (OR=1.93, 95%CI: 1.36 to 2.73, P = 0.0002) and a greater likelihood of discontinuing treatment due to trAEs (OR=2.07, 95%CI: 1.12 to 3.85, P = 0.02). There was no significant difference in the occurrence of severe trAEs leading to death (OR=1.36, 95%CI: 0.47 to 3.96, P = 0.57).ConclusionThis meta-analysis suggests that R/M-HNSCC patients receiving the combination of durvalumab and tremelimumab may achieve comparable outcomes in terms of ORR, DCR, OS, PFS, and DoR, without significant differences. However, the combination therapy is associated with a higher incidence of grade 3-4 trAEs and an increased likelihood of treatment discontinuation due to trAEs. These findings highlight the need for cautious consideration of the combination of durvalumab and tremelimumab in R/M-HNSCC patients, which should be further evaluated in high-quality studies.

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Immunotherapy in Head and Neck Cancer: Where Do We Stand?

Cited by 14 publications

References 102 publications

Pretreatment Circulating HPV16 DNA Viral Load Predicts Risk of Distant Metastasis in Patients with HPV16-Positive Oropharyngeal Cancer

Pretreatment Circulating HPV16 DNA Viral Load Predicts Risk of Distant Metastasis in Patients with HPV16-Positive Oropharyngeal Cancer

IL7 in combination with radiotherapy stimulates a memory T-cell response to improve outcomes in HNSCC models

Durvalumab with or without tremelimumab for patients with recurrent or metastatic squamous cell carcinoma of the head and neck: a systematic review and meta-analysis

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