Publications by authors named "Satu Salmio"

2 Publications

  • Page 1 of 1

Avelumab and cetuximab as a therapeutic combination: An overview of scientific rationale and current clinical trials in cancer.

Cancer Treat Rev 2021 Jun 2;97:102172. Epub 2021 Mar 2.

Medical Oncology, Department of Precision Medicine, Università degli Studi della Campania Luigi Vanvitelli, Naples, Italy.

Treatment outcomes have improved with the advent of immune checkpoint inhibitors and small molecule inhibitors. However, many patients do not respond with single agents. Consequently, ongoing research is focused on the use of combination therapies to increase clinical efficacy by potential synergistic effects. Here, we outline ongoing trials and review the rationale and evidence for the combination of avelumab, an anti-programmed death ligand 1 (PD-L1) immunoglobulin G1 (IgG1) monoclonal antibody (mAb), with cetuximab, an anti-epidermal growth factor receptor (EGFR) IgG1 mAb. Avelumab is approved as a monotherapy for the treatment of Merkel cell carcinoma and urothelial carcinoma, and in combination with axitinib for renal cell carcinoma; cetuximab is approved in combination with chemotherapy for the treatment of squamous cell carcinoma of the head and neck (SCCHN) and RAS wild-type metastatic colorectal cancer, and in combination with radiation therapy for SCCHN. Avelumab binds to PD-L1 expressed on tumor cells and immune regulatory cells, thus blocking its interaction with programmed death 1 and reventing T-cell suppression; cetuximab inhibits the EGFR signaling pathway, inhibiting proliferation and inducing apoptosis. Both therapies have complementary mechanisms of action and may also activate the immune system to induce innate effector function through the binding of their Fc regions to natural killer (NK) cells. Furthermore, cetuximab combined with chemotherapy has been shown to induce immunogenic cell death and leads to an increase in tumor-infiltrating CD8+ T and NK cells, which should synergize with the immunostimulatory effects of avelumab. Prospective studies will investigate this combination and inform future treatment strategies.
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http://dx.doi.org/10.1016/j.ctrv.2021.102172DOI Listing
June 2021

Treating Patients With Locally Advanced Squamous Cell Carcinoma of the Head and Neck Unsuitable to Receive Cisplatin-Based Therapy.

Front Oncol 2019 22;9:1522. Epub 2020 Jan 22.

Fondazione IRCCS Istituto Nazionale Tumori and University of Milan, Milan, Italy.

Concurrent chemoradiotherapy with high-dose cisplatin (100 mg/m every 3 weeks) is the preferred regimen with curative intent for patients with unresected locally advanced squamous cell carcinoma of the head and neck (LA SCCHN). This treatment is associated with acute and late toxicities, including myelosuppression, severe nausea/vomiting, irreversible renal failure, hearing loss, and neurotoxicity. Because of cisplatin's safety profile, treatment adherence to high-dose cisplatin can be suboptimal. Patients commonly receive less than the total cumulative target dose of 300 mg/m or the minimum recommended dose of 200 mg/m, which can have a negative impact on locoregional control and survival. Alternatively, cetuximab plus radiotherapy may be most suitable for patients at high risk of non-adherence to high-dose cisplatin. We discuss the baseline characteristics dictating the unsuitability/borderline unsuitability of cisplatin and the available alternative evidence-based treatment regimens for patients with LA SCCHN. We non-systematically reviewed published phase II and III trials and retrospective analyses of high-dose cisplatin-based chemoradiation in LA SCCHN conducted between 1987 and 2018, focusing on recent key phase III studies. We defined the baseline characteristics and associated prescreening tests to determine unsuitability and borderline unsuitability for high-dose cisplatin in combination with radiotherapy in patients with LA SCCHN. Patients with any pre-existing comorbidities that may be exacerbated by high-dose cisplatin treatment can be redirected to a non-cisplatin-based option to minimize the risk of treatment non-adherence. High-dose cisplatin plus radiotherapy remains the preferred treatment for fit patients with unresected LA SCCHN; patients who are unsuitable or borderline unsuitable for high-dose cisplatin could be identified using available tests for potential comorbidities and should be offered alternative treatments, such as cetuximab plus radiotherapy.
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http://dx.doi.org/10.3389/fonc.2019.01522DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6987395PMC
January 2020