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Systemic therapy for advanced cutaneous squamous cell carcinoma
Kelly Fitzgerald1, Katy K Tsai2
1University of California, San Francisco, San Francisco, California.
Abstract:
The incidence of advanced cutaneous squamous cell carcinoma (cSCC) is increasing; of the 1.3 million nonmelanoma skin cancers that arise each year, approximately 20% are cSCC, and between 2-5% of these cases ultimately metastasize. However, there is no established consensus on first-line systemic treatment for those patients who have locally advanced or metastatic disease. Major classes of systemic agents include chemotherapy, epidermal growth factor receptor (EGFR)-targeted therapy, and immunotherapy; each is associated with a distinct set of adverse effects, and availability of data from randomized controlled trials (RCTs) to definitively guide treatment are limited. While several chemotherapeutic agents have been described in case studies or small patient cohorts, only one RCT has been conducted, demonstrating a 34% overall response rate for a cisplatin-based regimen. EGFR-inhibitors evaluated for use in cSCC by RCT include cetuximab, panitumumab, and gefitinib; response rates ranged from 15-31% for these agents. Inhibitors of the immune checkpoint programmed death-1 (PD-1) have yielded promising outcomes in advanced cSCC; indeed, the PD-1 inhibitor cemiplimab recently received FDA approval for use in advanced cSCC. Despite these advances, the preferred regimen for systemic treatment of cSCC remains unclear, particularly in immunocompromised populations. Herein we provide a review of the literature supporting the use of these modalities and a discussion of their clinical utility.
Insights
Advanced cutaneous squamous cell carcinoma (cSCC) treatment lacks consensus. Systemic therapies like chemotherapy, EGFR-inhibitors, and immunotherapy show varied efficacy, with PD-1 inhibitors emerging as promising for advanced cSCC.
Area of Science:
- Oncology
- Dermatology
- Medical Research
Background:
- The incidence of advanced cutaneous squamous cell carcinoma (cSCC) is rising, with a significant percentage metastasizing.
- Current treatment guidelines for advanced or metastatic cSCC lack definitive consensus.
- Limited randomized controlled trial (RCT) data exists for systemic treatment options.
Purpose of the Study:
- To review the literature supporting systemic treatment modalities for advanced cSCC.
- To discuss the clinical utility of chemotherapy, epidermal growth factor receptor (EGFR)-targeted therapy, and immunotherapy.
- To address the ongoing uncertainty in preferred systemic regimens, especially for immunocompromised patients.
Main Methods:
- Literature review of studies on systemic treatments for advanced cSCC.
- Analysis of data from randomized controlled trials (RCTs), case studies, and patient cohorts.
- Discussion of treatment efficacy, adverse effects, and clinical applicability.
Main Results:
- Chemotherapy (e.g., cisplatin-based regimens) showed a 34% overall response rate in one RCT.
- EGFR-inhibitors (cetuximab, panitumumab, gefitinib) demonstrated response rates of 15-31% in RCTs.
- Programmed death-1 (PD-1) inhibitors, like cemiplimab, show promising outcomes and have received FDA approval for advanced cSCC.
Conclusions:
- While PD-1 inhibitors represent a significant advance, the optimal systemic treatment for advanced cSCC remains undetermined.
- Chemotherapy and EGFR-targeted therapies have demonstrated some efficacy but are limited by data and side effects.
- Further research is needed to establish clear treatment guidelines, particularly for specific patient populations.
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