Phase II Trial of Adjuvant Nivolumab Following Salvage Resection in Patients with Recurrent Squamous Cell Carcinoma of the Head and Neck

Leddon, Jennifer L.; Gulati, Shuchi; Haque, Sulsal; Allen, Casey L.; Palackdharry, Sarah; Mathews, Maria; Kurtzweil, Nicky; Riaz, Muhammed Kashif; Takiar, Vinita; Nagasaka, Misako; Patil, Yash; Zender, Chad; Tang, Alice; Cervenka, Brian; McGrath, Julie; Korn, W. Michael; Hinrichs, Benjamin H.; Jandarov, Roman; Harun, Nusrat; Sukari, Ammar; Wise‐Draper, Trisha M.

doi:10.1158/1078-0432.ccr-21-4554

Cited by 16 publications

(5 citation statements)

References 25 publications

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“…In the immunotherapy of head and neck cancer, it's reported that TMB was higher in responders compared with non-responders [35]. However, results from another ICI cohort containing 261 patients presented that TMB≥10 mut/Mb failed to predict both OS and disease-free survival [36]. Our present study demonstrated that the top 20% of TMB (≥9.51 mut/Mb) could predict OS in patients with ICI treatment, at which cutoff, TMB exhibited no predictive role for that without ICI therapy.…”

Section: (Which Was Not Certified By Peer Review)mentioning

confidence: 98%

High tumor mutational burden predicts survival and responses to ICI immunotherapy in a cancer-dependent manner

Tang,

Lan,

Liu

et al. 2023

Preprint

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ObjectiveHigh tumor mutational burden (TMB) is a promising biomarker for patients with immunotherapy in certain types of solid tumors. This article focuses on exploring possible universally optimal cutoffs of TMB for predicting immune checkpoint inhibitors (ICIs) response and prognosis for eight types of cancers.MethodsThe present study collected eight types of tumors including 2767 patients receiving immune checkpoint inhibitors (ICIs) treatment and 14862 patients without ICI treatment. We tried to explore optimal cutoffs of TMB in each type of tumor via selecting several possible cutoffs of TMB including 10mut/Mb, top 10%, 20%, and 30% of TMB within each histology.ResultsWe found that there was a significant difference in TMB values between ICI-treated and non-ICI-treated groups. The cutoff of TMB appropriate for predicting response rates, progression rates, and survival rates was varied in ICI therapy patients. Moreover, the optimal cutoff of TMB for predicting progression-free survival and overall survival in different types of the tumor was also quietly different.ConclusionOur current study suggested that TMB predicts prognosis and responses to ICI treatment in a cancer-dependent manner.

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Section: (Which Was Not Certified By Peer Review)mentioning

confidence: 98%

High tumor mutational burden predicts survival and responses to ICI immunotherapy in a cancer-dependent manner

Tang,

Lan,

Liu

et al. 2023

Preprint

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“…All 20 studies reported the incidences of any grade and grade three or more trAEs (Table 1). Nine studies were anti-PD1 monotherapy, [3][4][5][14][15][16][17][18][19] eight studies were anti-PDL1 monotherapy, 6,7,[20][21][22][23][24][25] seven studies were ICIs combination therapy, [6][7][8]14,20,26,27 five studies were median duration of treatment ≤3months, eight studies were >3 months, nine studies were RCT, and 11 studies were non-RCT. Seventeen studies reported the incidence of treatment-related deaths, among which eight studies were anti-PD1 monotherapy, eight studies were anti-PDL1 monotherapy, and six studies were ICIs combination therapy.…”

Section: Study Characteristics and Quality Assessmentmentioning

confidence: 99%

Toxicity profiles of immune checkpoint inhibitors for recurrent or metastatic head and neck squamous cell carcinoma: A systematic review and meta‐analysis

Dang,

Li,

Liu

et al. 2024

Cancer Medicine

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BackgroundImmune checkpoint inhibitors (ICIs) are widely used in recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC); however, the toxicity profiles are inconclusive.MethodsClinical trials evaluating ICIs for R/M HNSCC were searched from online databases. The characteristics of the studies and the results of incidences of any grade treatment‐related adverse events (trAEs), grade three or more trAEs, treatment‐related deaths, trAEs leading to discontinuation of treatment, and specific trAEs were extracted.ResultsTwenty studies with 3756 patients were included. The pooled incidences of any grade trAEs, grade three or more trAEs, treatment‐related deaths, trAEs leading to discontinuation of treatment for overall population were 62.07% (95% CI, 59.07%–65.02%), 13.82% (95% CI, 11.23%–16.62%), 0.39% (95% CI, 0.15%–0.71%), 3.99% (95% CI, 2.36%–5.95%), respectively. Programmed cell death protein 1 (PD‐1) inhibitors monotherapy and ICIs combination therapy had significantly higher incidences of any grade trAEs (odds ratio [OR], 1.25, 95% CI, 1.05–1.49 and 1.36, 95% CI, 1.15–1.60, respectively), grade three or more trAEs (OR, 1.41, 95% CI, 1.08–1.84 and 1.79, 95% CI, 1.39–2.30, respectively), trAEs leading to discontinuation of treatment (OR, 3.98, 95% CI, 2.06–7.70 and 10.14, 95% CI, 5.49–18.70, respectively) compared with programmed death‐ligand 1 (PD‐L1) inhibitors monotherapy. ICIs combination therapy had a significantly higher incidence of grade three or more trAEs compared with PD‐1 inhibitors monotherapy (OR, 1.27, 95% CI, 1.03–1.55); however, the incidences of any grade trAEs and trAEs leading to discontinuation of treatment were not significant different.ConclusionsOur study suggests that the incidences of grade three or more trAEs, treatment‐related deaths, and trAEs leading to discontinuation of treatment are low in R/M HNSCC patients treated with ICIs. PD‐L1 inhibitors monotherapy may be safer compared with PD‐1 inhibitors monotherapy and ICIs combination therapy.

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“…Adjuvant PD-1 blockade immunotherapy in combination with salvage surgery is being evaluated in multiple clinical trials as a means of improving the overall survival of patients with recurrent or metastatic HNSCC [100,101]. Surgery in this context functions as previously described by reducing tumor bulk and leaving a lesser amount of cancerous tissue for the immune system to combat.…”

Section: Salvage Surgerymentioning

confidence: 99%

“…The adjuvant PD-1 blockade in this context then promotes the removal of immunosuppressive barriers to immune response against residual cancer cells. A recent phase II clinical trial has shown a tolerable safety profile and improved disease-free survival compared to historical control samples at two-year follow-up [101].…”

Section: Salvage Surgerymentioning

confidence: 99%

Mechanisms of Resistance and Therapeutic Perspectives in Immunotherapy for Advanced Head and Neck Cancers

Meci,

Goyal,

Slonimsky

2024

Cancers

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Immunotherapy is emerging as an effective treatment for advanced head and neck cancers and interest in this treatment modality has led to rapid expansion of this research. Pembrolizumab and nivolumab, monoclonal antibodies directed against the programmed cell death-1 (PD-1) receptor, are US Food and Drug Administration (FDA)- and European Medical Agency (EMA)-approved immunotherapies for head and neck squamous cell carcinoma (HNSCC). Resistance to immunotherapy is common, with about 60% of patients with recurrent or metastatic HNSCC not responding to immunotherapy and only 20–30% of patients without disease progression in the long term. Overcoming resistance to immunotherapy is therefore essential for augmenting the effectiveness of immunotherapy in HNSCC. This review details the innate and adaptive mechanisms by which head and neck cancers can become resistant to immunotherapeutic agents, biomarkers that can be used for immunotherapy patient selection, as well as other factors of the tumor microenvironment correlated with therapeutic response and prognosis. Numerous combinations and novel immunotherapies are currently being trialed, based on better understood immune evasion mechanisms. These potential treatments hold the promise of overcoming resistance to immunotherapy in head and neck cancers.

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Phase II Trial of Adjuvant Nivolumab Following Salvage Resection in Patients with Recurrent Squamous Cell Carcinoma of the Head and Neck

Cited by 16 publications

References 25 publications

High tumor mutational burden predicts survival and responses to ICI immunotherapy in a cancer-dependent manner

High tumor mutational burden predicts survival and responses to ICI immunotherapy in a cancer-dependent manner

Toxicity profiles of immune checkpoint inhibitors for recurrent or metastatic head and neck squamous cell carcinoma: A systematic review and meta‐analysis

Mechanisms of Resistance and Therapeutic Perspectives in Immunotherapy for Advanced Head and Neck Cancers

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