Cetuximab is efficient and safe in patients with advanced cutaneous squamous cell carcinoma: a retrospective, multicentre study

Abstract

There is no standard of care for unresectable cutaneous squamous cell carcinoma (cSCC). Chemotherapy, alone or combined with radiotherapy, is commonly used mostly as palliative treatment; moreover, its poor safety profile limits its use most of the time, especially in elderly patients. Thus, alternative options are needed. Targeted molecular inhibitors, such as the epidermal growth factor receptor inhibitor cetuximab, seem promising, but data are limited. We retrospectively evaluated clinical outcomes of cetuximab as a single agent in this indication. The primary endpoint was the Disease Control Rate (DCR) at 6 weeks according to RECIST criteria. Secondary endpoints included DCR at 12 weeks, objective response rate (ORR) at 6 and 12 weeks, progression-free-survival (PFS), overall survival (OS), and safety profile. Fifty-eight patients received cetuximab as monotherapy. The median age was 83.2 (range, 47.4 to 96.1). The majority of patients was chemotherapy naïve. The median www.oncotarget.com

Improved therapeutic efficacy of unmodified anti-tumor antibodies by immune checkpoint blockade and kinase targeted therapy in mouse models of melanoma

“…Moreover, we showed that treatment with TA99 induced a greater DC infiltrate in B16 tumors. This finding is consistent with reports indicating that treatment with the anti-EGFR antibody cetuximab results in an increased NK cell mediated ADCC, which makes the tumor cells or their antigens more susceptible to phagocytosis by DC [ 16 , 17 ]. Further, it has been reported that resistance to immunotherapy may be due in part to defective recruitment of DC, downregulation of antigen processing and presentation, and thus reduced cross-priming [ 24 , 35 – 37 ].…”

“…Targeting tumor antigens with specific antibodies, such as anti-CD20 (rituximab), anti-HER2 (trastuzumab), anti-EGFR (cetuximab), is well-established and has been relatively successful in a number of cancers, via interference with cellular signaling, complement-mediated lysis, antibody-dependent cell-mediated cytotoxicity (ADCC), and/or antibody-dependent cell phagocytosis (ADDP) [ 12 – 14 , 16 , 17 ]. However, the use of these unmodified antibodies during the therapy of advanced solid tumors such as breast cancer, metastatic colorectal cancer and head and neck squamous cell carcinomas as monotherapy, result in a high proportion of tumors with primary and acquired resistance, and relatively low rates of lasting therapeutic responses [ 18 – 20 ].…”

Comprehensive Mutational and Phenotypic Characterization of New Metastatic Cutaneous Squamous Cell Carcinoma Cell Lines Reveal Novel Drug Susceptibilities

“…Interestingly, some PI3K inhibitors produced little to no response against the cell lines, a likely result of isoform specificity that requires further investigation [ 33 ]. The anti-EGFR biologic Cetuximab is sometimes given to patients with advanced cSCC, achieving overall response rates approaching 50% [ 49 ]. However, there are multiple mechanisms by which downstream effectors of EGFR may become activated, including via PI3K [ 50 ].…”

Cutaneous Squamous Cell Carcinoma: From Pathophysiology to Novel Therapeutic Approaches

“…The objective response rate (ORR) was 53% and 42%, respectively, at 6 and 12 weeks. The median progression-free survival (PFS) and overall survival were 9.7 months and 17.5 months, respectively [ 163 ].…”