Phase I Trial of Cemiplimab, Radiotherapy, Cyclophosphamide, and Granulocyte Macrophage <scp>Colony-Stimulating</scp> Factor in Patients with Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma

Babiker, Hani M.; Braña, Irene; Mahadevan, Daruka; Owonikoko, Taofeek K.; Calvo, Emiliano; Rischin, Danny; Moreno, Víctor; Papadopoulos, Kyriakos P.; Crittenden, Marka R.; Formenti, Silvia C.; Giralt, Jordi; Garrido, Pilar; Soria, Ainara; Hervás-Morón, Asunción; Mohan, Kosalai Kal; Fury, Matthew G.; Lowy, Israel; Mathias, Melissa; Ma, Feng; Li, Jingjin; Stankevich, Elizabeth

doi:10.1002/onco.13810

Cited by 17 publications

(10 citation statements)

References 17 publications

(22 reference statements)

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“…Another case report innovatively used triple-combination therapy in esophageal squamous cell carcinoma (ESCC) and obtained short-term benefits, but the patient died of severe pneumonia ( 43 ). A Phase I trial of cemiplimab, radiotherapy, cyclophosphamide, and GM-CSF in patients with recurrent or metastatic head and neck squamous cell carcinoma, did not demonstrate higher efficacy than other PD-1 inhibitor monotherapies but showed tolerability of the regimen, and the most common treatment-emergent adverse events (TEAEs) included fatigue (40%), constipation (26.7%), asthenia, dyspnea, maculopapular rash, and pneumonia (20% each) ( 44 ). The SWORD trial reported the preliminary results of feasibility and safety of the triple combination of a PD-1/PD-L1 inhibitor, SBRT and GM-CSF in advanced solid tumors ( 45 ).…”

Section: Discussionmentioning

confidence: 99%

Anti-PD-1 Immunotherapy Combined With Stereotactic Body Radiation Therapy and GM-CSF as Salvage Therapy in a PD-L1-Positive Patient With Refractory Metastatic Thyroid Hürthle Cell Carcinoma: A Case Report and Literature Review

et al. 2021

Front. Oncol.

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Thyroid Hürthle cell carcinoma, known as thyroid eosinophilic carcinoma, is a rare pathological type of differentiated thyroid cancer (DTC), representing 3-4% of all thyroid cancers. However, given the high risk of invasion and metastasis, thyroid Hürthle cell carcinoma has a relatively poor prognosis. Traditional treatment methods have limited effects on patients with metastatic thyroid cancers. Developing a valuable therapy for advanced thyroid carcinomas is an unfilled need, and immunotherapy could represent another choice for these tumors. We herein reported the case of a patient with recurrent advanced thyroid Hürthle cell cancer and positive programmed death-ligand 1 (PD-L1) expression, who suffered tumor progression after re-surgery, radiotherapy, and targeted therapy. It is encouraging that PD-1 inhibitors in combination with GM-CSF and stereotactic body irradiation (SBRT) on metastatic disease have a significant anti-tumor effect.

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Section: Discussionmentioning

confidence: 99%

Anti-PD-1 Immunotherapy Combined With Stereotactic Body Radiation Therapy and GM-CSF as Salvage Therapy in a PD-L1-Positive Patient With Refractory Metastatic Thyroid Hürthle Cell Carcinoma: A Case Report and Literature Review

et al. 2021

Front. Oncol.

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“…Additionally, CTLA-4 inhibitors monotherapy as well as combination therapy with CTLA-4 inhibitors and either gemcitabine or cyclophosphamide showed promising results in BC and also CRC mouse models [89]. The phase 1 clinical trial of 15 patients with refractory and metastatic HNSCC showed that combination therapy of cyclophosphamide and radiation therapy in combination with GM-CSF (granulocyte macrophage-colonystimulating factor) could demonstrate significant therapeutic benefit [90]. Recent research demonstrated that treatment with PD-L1 and CTLA-4 inhibitors in conjunction with cancer stem cell-pulsed dendritic cells (CSC-DC) improved T cell proliferation, inhibited TGF-β secretion, intensified IFN-γ secretion, and improved host-specific CD8 + T cell response versus CSCs in B16-F10 mice melanoma tumour model [91].…”

Section: Ctla-4 Inhibitormentioning

confidence: 99%

Immune Checkpoint Inhibitors in Cancer Therapy

et al. 2022

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The discovery of immune checkpoint proteins such as PD-1/PDL-1 and CTLA-4 represents a significant breakthrough in the field of cancer immunotherapy. Therefore, humanized monoclonal antibodies, targeting these immune checkpoint proteins have been utilized successfully in patients with metastatic melanoma, renal cell carcinoma, head and neck cancers and non-small lung cancer. The US FDA has successfully approved three different categories of immune checkpoint inhibitors (ICIs) such as PD-1 inhibitors (Nivolumab, Pembrolizumab, and Cemiplimab), PDL-1 inhibitors (Atezolimumab, Durvalumab and Avelumab), and CTLA-4 inhibitor (Ipilimumab). Unfortunately, not all patients respond favourably to these drugs, highlighting the role of biomarkers such as Tumour mutation burden (TMB), PDL-1 expression, microbiome, hypoxia, interferon-γ, and ECM in predicting responses to ICIs-based immunotherapy. The current study aims to review the literature and updates on ICIs in cancer therapy.

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“…Notwithstanding, some tumor-bearing mice advanced spontaneous metastases under continuous treatment with combined regimen [ 142 ]. Moreover, a phase 1 clinical trial in 15 patients with refractory and metastatic HNSCC indicated that combination therapy with PD-1 inhibitor cemiplimab plus cyclophosphamide, radiation therapy (RT), and granulocyte–macrophage colony-stimulating factor (GM-CSF) could demonstrate acceptable safety profile [ 143 ]. However, the regimen resulted in no significant effects compared to the monotherapy with cemiplimab.…”

Section: Combination Therapy Using Icismentioning

confidence: 99%

Combination therapy with immune checkpoint inhibitors (ICIs); a new frontier

et al. 2022

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Recently, immune checkpoint inhibitors (ICIs) therapy has become a promising therapeutic strategy with encouraging therapeutic outcomes due to their durable anti-tumor effects. Though, tumor inherent or acquired resistance to ICIs accompanied with treatment-related toxicities hamper their clinical utility. Overall, about 60–70% of patients (e.g., melanoma and lung cancer) who received ICIs show no objective response to intervention. The resistance to ICIs mainly caused by alterations in the tumor microenvironment (TME), which in turn, supports angiogenesis and also blocks immune cell antitumor activities, facilitating tumor cells' evasion from host immunosurveillance. Thereby, it has been supposed and also validated that combination therapy with ICIs and other therapeutic means, ranging from chemoradiotherapy to targeted therapies as well as cancer vaccines, can capably compromise tumor resistance to immune checkpoint blocked therapy. Herein, we have focused on the therapeutic benefits of ICIs as a groundbreaking approach in the context of tumor immunotherapy and also deliver an overview concerning the therapeutic influences of the addition of ICIs to other modalities to circumvent tumor resistance to ICIs.

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Phase I Trial of Cemiplimab, Radiotherapy, Cyclophosphamide, and Granulocyte Macrophage Colony-Stimulating Factor in Patients with Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma

Abstract: Background. Refractory and metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) generally does not respond to PD-1 inhibitor monotherapy. Cemiplimab is a human anti-PD-1 monoclonal antibody. An expansion

Cited by 17 publications

References 17 publications

Anti-PD-1 Immunotherapy Combined With Stereotactic Body Radiation Therapy and GM-CSF as Salvage Therapy in a PD-L1-Positive Patient With Refractory Metastatic Thyroid Hürthle Cell Carcinoma: A Case Report and Literature Review

Anti-PD-1 Immunotherapy Combined With Stereotactic Body Radiation Therapy and GM-CSF as Salvage Therapy in a PD-L1-Positive Patient With Refractory Metastatic Thyroid Hürthle Cell Carcinoma: A Case Report and Literature Review

Immune Checkpoint Inhibitors in Cancer Therapy

Combination therapy with immune checkpoint inhibitors (ICIs); a new frontier

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