Targeted Therapies and Immune-Checkpoint Inhibition in Head and Neck Squamous Cell Carcinoma: Where Do We Stand Today and Where to Go?

Grün, Jens von der; Rödel, Franz; Brandts, Christian; Fokas, Emmanouil; Gückenberger, Matthias; Rödel, Claus; Balermpas, Panagiotis

doi:10.3390/cancers11040472

Cited by 24 publications

(16 citation statements)

References 143 publications

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“…Currently, following the KEYNOTE-048 trial, many prospective trials are ongoing in an attempt to evaluate the front-line use of ICIs [ 14 ]. Therefore, considering the treatment outcomes of subsequent cetuximab therapies after immunotherapy is essential.…”

Section: Introductionmentioning

confidence: 99%

Safety and efficacy of cetuximab-containing chemotherapy after immune checkpoint inhibitors for patients with squamous cell carcinoma of the head and neck: a single-center retrospective study

Kurosaki¹,

Mitani²,

Tanaka³

et al. 2020

Anti-Cancer Drugs

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Immunotherapy has been shown to prolong survival in recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) in front-line use; however, subsequent systemic therapy has not been optimized. This study aimed to evaluate the safety and efficacy of cetuximab-containing chemotherapy after immunotherapy. We retrospectively analyzed patients with recurrent or metastatic SCCHN who underwent cetuximab-containing regimens after progression on immunotherapy. Of the 22 patients who met the inclusion criteria, 21 received paclitaxel and cetuximab, and 1 carboplatin and fluorouracil and cetuximab after immunotherapy. Nine patients achieved a partial response, 10 patients had stable disease as their best response on cetuximab-containing chemotherapy, yielding an overall response rate and disease control rate of 40.9 and 86.4%, respectively. The median progression-free survival was 5.2 months, and the median overall survival was 14.5 months. Ten patients developed grade 3–4 adverse events, including neutropenia (31.8%), acneiform rash (9.1%), anemia (4.5%), hypertransaminasemia (4.5%) and stomatitis (4.5%). The most frequent cetuximab-related toxicities across all grades were skin reactions (77.3%), hypomagnesemia (40.9%), stomatitis (27.3%), paronychia (13.6%) and keratitis (4.5%). There was no treatment-related death. Taken together, cetuximab-containing chemotherapy was effective and feasible even after immunotherapy.

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Section: Introductionmentioning

confidence: 99%

Safety and efficacy of cetuximab-containing chemotherapy after immune checkpoint inhibitors for patients with squamous cell carcinoma of the head and neck: a single-center retrospective study

Kurosaki¹,

Mitani²,

Tanaka³

et al. 2020

Anti-Cancer Drugs

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“…Improved clinical outcomes have been achieved for a number of solid and hematological diseases treated with immune checkpoint blockade (ICB) targeting cytotoxic T lymphocyte associated protein (CTLA)-4 and programmed cell death 1 (PD-1) or its ligand PD-L1 [1][2][3][4][5][6][7][8][9][10][11]. Nevertheless, a large proportion of ICB-treated cancer patients still do not benefit from these drugs.…”

Section: Introductionmentioning

confidence: 99%

LAG3: The Biological Processes That Motivate Targeting This Immune Checkpoint Molecule in Human Cancer

Solinas

Migliori

Silva

et al. 2019

Cancers

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The programmed cell death 1 (PD-1) pathway is an important regulator of immune responses in peripheral tissues, including abnormal situations such as the tumor microenvironment. This pathway is currently the principal target for immunotherapeutic compounds designed to block immune checkpoint pathways, with these drugs improving clinical outcomes in a number of solid and hematological tumors. Medical oncology is experiencing an immune revolution that has scientists and clinicians looking at alternative, non-redundant inhibitory pathways also involved in regulating immune responses in cancer. A variety of targets have emerged for combinatorial approaches in immune checkpoint blockade. The main purpose of this narrative review is to summarize the biological role of lymphocyte activation gene 3 (LAG3), an emerging targetable inhibitory immune checkpoint molecule. We briefly discuss its role in infection, autoimmune disease and cancer, with a more detailed analysis of current data on LAG3 expression in breast cancer. Current clinical trials testing soluble LAG3 immunoglobulin and LAG3 antagonists are also presented in this work.

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“…In oral squamous cell carcinomas (OSCC), surgery with on indication followed by (chemo)radiotherapy is the first choice of treatment, whereas in most other sites in the head and neck region, (chemo)radiation is the first choice. Furthermore, for locally advanced and recurrent diseases, several advances to treat them with molecular targeted therapies have been made [4]. Despite these advances, treatment is often not effective in many patients, while still causing significant toxicity.…”

Section: Introductionmentioning

confidence: 99%

Imaging angiogenesis in patients with head and neck squamous cell carcinomas by [68Ga]Ga-DOTA-E-[c(RGDfK)]2 PET/CT

Lobeek

Rijpkema

Terry

et al. 2020

Eur J Nucl Med Mol Imaging

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Purpose Angiogenesis plays an important role in the growth and metastatic spread of solid tumours and is characterised by the expression of integrins on the cell surface of endothelial cells. Radiolabelled RGD peptides specifically target angiogenesis-related α v β 3 integrins, expressed on the activated endothelial cells of sprouting blood vessels. Here, we validated the feasibility of 68 Ga[Ga]-DOTA-E-[c(RGDfK)] 2 (68 Ga-RGD) PET/CT to visualise angiogenesis in patients with oral squamous cell carcinoma (OSCC). Methods Ten patients with OSCC and scheduled for surgical resection including elective neck dissection received an intravenously administration of 68 Ga-RGD (42 ± 8 μg; 214 ± 9 MBq). All patients subsequently underwent dynamic (n = 5) or static PET/CT imaging (n = 5) for 60 min or for 4 min/bed position at 30, 60 and 90 min after injection, respectively. Quantitative tracer uptake in tumour lesions was expressed as standardised uptake values (SUV). Additionally, tumour tissue was immunohistochemically stained for α v β 3 integrin to assess the expression pattern. Results 68 Ga-RGD tumour accumulation was observed in all patients. At 60 min post injection, tumour SUV max ranged between 4.0 and 12.7. Tracer accumulation in tumour tissue plateaued at 10 min after injection. Uptake in background tissue did not change over time, resulting in tumour-to-muscle tissue of 6.4 ± 0.7 at 60 min post injection. Conclusions 68 Ga-RGD PET/CT of α v β 3 integrin expression in OSCC patients is feasible with adequate tumour-to-background ratios. It will provide more insight in angiogenesis as a hallmark of the head and neck squamous cell carcinomas' tumour microenvironment. Trial registration https://eudract.ema.europa.eu no. 2015-000917-31 Keywords RGD-PET/CT. Angiogenesis. Squamous cell carcinoma. Head and neck cancer. α v β 3 integrin This article is part of the Topical Collection on Oncology-Head and Neck Electronic supplementary material The online version of this article (

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Targeted Therapies and Immune-Checkpoint Inhibition in Head and Neck Squamous Cell Carcinoma: Where Do We Stand Today and Where to Go?

Cited by 24 publications

References 143 publications

Safety and efficacy of cetuximab-containing chemotherapy after immune checkpoint inhibitors for patients with squamous cell carcinoma of the head and neck: a single-center retrospective study

Safety and efficacy of cetuximab-containing chemotherapy after immune checkpoint inhibitors for patients with squamous cell carcinoma of the head and neck: a single-center retrospective study

LAG3: The Biological Processes That Motivate Targeting This Immune Checkpoint Molecule in Human Cancer

Imaging angiogenesis in patients with head and neck squamous cell carcinomas by [68Ga]Ga-DOTA-E-[c(RGDfK)]2 PET/CT

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