Pembrolizumab Given Concomitantly with Chemoradiation and as Maintenance Therapy for Locally Advanced Head and Neck Squamous Cell Carcinoma: KEYNOTE-412

Machiels, Jean‐Pascal; Tao, Yungan; Burtness, Barbara; Tahara, Makoto; Licitra, Lisa; Rischin, Danny; Waldron, John; Simon, Christian; Grégoire, Vincent; Harrington, Kevin; Alves, Gustavo Vasconcelos; Lima, Iane Pinto Figueiredo; Pointreau, Y.; Hughes, Brett; Aksoy, Sercan; Hetnał, Marcin; Ge, Joy Yang; Brown, Holly; Cheng, Jonathan D.; Bidadi, Behzad; Siu, Lillian L.

doi:10.2217/fon-2020-0184

Cited by 48 publications

(28 citation statements)

References 16 publications

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“…Cetuximab, a monoclonal antibody targeting epidermal growth factor receptor, has also been shown to be a tolerated and effective regimen for maintenance therapy in recurrent metastatic HNSCC 43 , 44 . Immune check point inhibitors, such as pembrolizumab for PD-L1 high OSCC, are another type of agents in ongoing clinical trials for maintenance adjuvant therapy in locally advanced HNSCC 45 . For the investigation of the efficacy of these maintenance adjuvant therapies, proper selection of patients at high risk of disease relapse is fundamental in study design.…”

Section: Discussionmentioning

confidence: 99%

Perineural invasion/lymphovascular invasion double positive predicts distant metastasis and poor survival in T3–4 oral squamous cell carcinoma

Ting

Lee

et al. 2021

Sci Rep

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Postoperative adjuvant therapy has been indicated by advanced T classification for T3–4 oral squamous cell carcinoma (OSCC) and the significance of perineural invasion (PNI) and lymphovascular invasion (LVI) in treatment for T3–4 OSCC remains unclear. Ninety-eight cumulative patients with T3–4 OSCC who underwent curative surgery between Jan 2002 and Dec 2010 were recruited and analyzed. Twenty-seven (27.6%) patients were PNI/LVI double positive. PNI/LVI double positive demonstrated independent predictive values for higher neck metastasis (LN+), higher distant metastasis (DM) and low 5-year disease-specific survival (DSS) rates (p < 0.001, p = 0.017, and p < 0.001, respectively) after controlling for other pathologic features of the primary tumors. A high DM rate of 33.3% was noted in PNI/LVI double-positive patients. Among the PNI/LVI double negative, single positive to double positive subgroups, increasing LN+, DM rates and decreasing DSS rate were observed. Among the 44 LN+ patients, PNI/LVI double positive remained associated with a markedly high DM rate of 42.9% and a poor 5-year DSS of 27.7%. PNI/LVI double positive plays important roles in prognostication and potential clinical application for T3–4 OSCC by independently predicting LN+, DM, and poor DSS, and can be used as a good marker to select DM high-risk patients for novel adjuvant therapy trials.

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Section: Discussionmentioning

confidence: 99%

Perineural invasion/lymphovascular invasion double positive predicts distant metastasis and poor survival in T3–4 oral squamous cell carcinoma

Ting

Lee

et al. 2021

Sci Rep

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“…The primary hypothesis is that Pembrolizumab given in combination with SoC CRT is superior in event-free survival (disease progression or death in a maximum time frame of five years) than the SoC CRT. The investigators plan to complete the study by 2023 and believe that this trial may elucidate Pembrolizumab’s role when added to SoC in patients for whom five-year survival rates are poor, besides gaining insight on factors that influence the efficacy of immunotherapy by studying biomarkers data [ 98 ].…”

Section: Immune Checkpoint Blockade (Icb) In Hnscc Treatmentmentioning

confidence: 99%

Immune Checkpoints Pathways in Head and Neck Squamous Cell Carcinoma

Veigas

Mahmoud

Merlo

et al. 2021

Cancers

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Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous group of tumors usually diagnosed at an advanced stage and characterized by a poor prognosis. The main risk factors associated with its development include tobacco and alcohol consumption and Human Papillomavirus (HPV) infections. The immune system has a significant role in the oncogenesis and evolution of this cancer type. Notably, the immunosuppressive tumor microenvironment triggers immune escape through several mechanisms. The improved understanding of the antitumor immune response in solid tumors and the role of the immune checkpoint molecules and other immune regulators have led to the development of novel therapeutic strategies that revolutionized the clinical management of HNSCC. However, the limited overall response rate to immunotherapy urges identifying predictive biomarkers of response and resistance to treatment. Here, we review the role of the immune system and immune checkpoint pathways in HNSCC, the most relevant clinical findings linked to immunotherapeutic strategies and predictive biomarkers of response and future treatment perspectives.

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“…In terms of LA disease, a phase Ib study with 59 patients assessed pembrolizumab with weekly cisplatin-based CRT and demonstrated a favorable toxicity profile, with an end of treatment complete response of 85.3% and 78.3% based on imaging in HPV positive and negative groups, respectively [ 91 ]. Currently, a phase III trial KEYNOTE-412 is ongoing and is assessing pembrolizumab with CRT in LA SCCHN (NCT03040999) [ 92 ]. In addition, a trial assessing dual ICI blockade with RT in LA SCCHN is actively recruiting patients (NCT03426657).…”

Section: Current Applications Of Egfr Inhibition In Scchn In the Era Of Immunotherapymentioning

confidence: 99%

Current Aspects and Future Considerations of EGFR Inhibition in Locally Advanced and Recurrent Metastatic Squamous Cell Carcinoma of the Head and Neck

Patel

Saba

2021

Cancers

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Recurrent metastatic (RM) and locally advanced (LA) squamous cell carcinoma of the head and neck (SCCHN) are devasting disease states with limited therapeutic options and poor overall survival. Targeting the epidermal growth factor receptor (EGFR) is one area that has helped improve outcomes in this disease. Anti-EGFR based therapies have been shown to improve overall survival and mitigate the significant toxicities incurred from standard radiation, chemotherapy, and/or surgical options. Cetuximab, the most well-studied anti-EGFR monoclonal antibody, has demonstrated a positive impact on outcomes for RM and LA SCCHN. However, the development of early resistance to cetuximab highlights the need for a wider arsenal of therapy for RM and LA diseases. The use of immune checkpoint inhibitors has recently transformed the treatment of recurrent SCCHN. Drugs such as pembrolizumab and nivolumab have demonstrated success in recent clinical trials and have been approved for the treatment of advanced disease. Given the positive results of both EGFR targeted agents and immune checkpoint inhibitors, ongoing trials are studying their synergistic effects.

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Pembrolizumab Given Concomitantly with Chemoradiation and as Maintenance Therapy for Locally Advanced Head and Neck Squamous Cell Carcinoma: KEYNOTE-412

Cited by 48 publications

References 16 publications

Perineural invasion/lymphovascular invasion double positive predicts distant metastasis and poor survival in T3–4 oral squamous cell carcinoma

Perineural invasion/lymphovascular invasion double positive predicts distant metastasis and poor survival in T3–4 oral squamous cell carcinoma

Immune Checkpoints Pathways in Head and Neck Squamous Cell Carcinoma

Current Aspects and Future Considerations of EGFR Inhibition in Locally Advanced and Recurrent Metastatic Squamous Cell Carcinoma of the Head and Neck

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