Review of systemic agents in the treatment of advanced cutaneous squamous cell carcinoma

2019 ◽  
Vol 15 (27) ◽  
pp. 3171-3184 ◽  
Author(s):  
Erik T Petersen ◽  
Saqib R Ahmed ◽  
Leon Chen ◽  
Sirunya Silapunt ◽  
Michael R Migden
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Treatment Options ◽  
Poor Response ◽  
Cutaneous Squamous Cell Carcinoma ◽  
Significant Treatment ◽  
Fda Approval ◽  
Us Fda ◽  
First Time

Advanced cutaneous squamous cell carcinoma (cSCC) accounts for only 5% of all cases of cSCC but up to 60% of disease related deaths. Historically, this disease has lacked effective treatment options due to a combination of poor response rate, poor response durability and significant treatment-associated morbidity. Autumn of 2018 marked the first time ever that an agent received US FDA approval for advanced cSCC and the future is looking much brighter for this previously neglected patient population. The purpose of this article is to review the various systemic treatment options for advanced cSCC moving from the past to the present, highlighting their relative merits and shortcomings, and to briefly speculate on future developments in the field of advanced cSCC.

scholarly journals An online review of informational sources for advanced or high-risk cutaneous squamous cell carcinoma

2021 ◽  
Author(s):  
Rachel Starkings ◽  
Valerie Shilling ◽  
Lesley Fallowfield
Keyword(s):  
Squamous Cell Carcinoma ◽  
High Risk ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Advanced Disease ◽  
Treatment Options ◽  
Cutaneous Squamous Cell Carcinoma ◽  
Online Information ◽  
Eligibility Criteria ◽  
Treatment Pathways

Abstract Objective Cutaneous squamous cell carcinoma (cSCC) is one of the most prevalent non-melanoma skin cancers worldwide. While usually treatable, patients with high-risk or advanced disease have few treatment options and limited resources available. This review assesses what online information resources are available to patients and their families about either high-risk or advanced cSCC. Methods Searches were run, via Google, using 8 terms such as ‘advanced cutaneous squamous cell carcinoma patient information’. Advertisements were removed and the first 3 pages/30 results from each search were screened for duplicates and then against eligibility criteria. Websites needed to have been updated within the past 5 years, be freely accessible, designed specifically for patients and refer to the advanced disease or high-risk setting. Remaining results were assessed using the DISCERN tool. Results Of the final 240 results, 121 were duplicates and 104 were ineligible. The remaining 15 sources were predominantly aimed at American audiences, used variable terminology and revealed differing treatment pathways. Only 3 sites were deemed as ‘high’-quality information sources. Conclusion There is a lack of accessible online information on high-risk or advanced cSCC for patients. What is available is often too scientific or clinical and lacks clarity about the disease and treatment options. Practice Implications Further work is needed to improve the integrity and accessibility of online sources and to signpost patients to the most reliable information. This should include elements of patient led research, clinical education and information development.

Treatment of advanced cutaneous squamous cell carcinoma: a Mohs surgery and dermatologic oncology perspective

2021 ◽  
Author(s):  
Kelly M Wilmas ◽  
Quoc-Bao Nguyen ◽  
Jigar Patel ◽  
Sirunya Silapunt ◽  
Michael R Migden
Keyword(s):  
Squamous Cell Carcinoma ◽  
Radiation Therapy ◽  
Antitumor Activity ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Treatment Options ◽  
Locally Advanced ◽  
Cutaneous Squamous Cell Carcinoma ◽  
Durable Response ◽  
Alternative Approach

Locally advanced or metastatic cutaneous squamous cell carcinoma no longer amenable to surgical resection or primary radiation therapy requires an alternative approach to treatment. Until 2018, management consisted of limited systemic chemotherapies, which carried marginal clinical benefit. The introduction of immunotherapy with anti-PD-1 antibodies resulted in alternative treatment options for advanced cutaneous squamous cell carcinoma with substantial antitumor activity, durable response and acceptable safety profile. The field of immunotherapeutics continues to expand with adjuvant, neoadjuvant and intralesional studies currently in progress. Herein, the authors discuss their approach for the treatment of advanced cutaneous squamous cell carcinoma from the perspective of a Mohs surgeon and a dermatologic oncologist.

scholarly journals Cutaneous Squamous Cell Carcinoma of the Head and Neck

2011 ◽  
Vol 2011 ◽  
pp. 1-10 ◽  
Author(s):  
Vivek V. Gurudutt ◽  
Eric M. Genden
Keyword(s):  
Squamous Cell Carcinoma ◽  
High Risk ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Complex Disease ◽  
Treatment Options ◽  
Cutaneous Squamous Cell Carcinoma ◽  
Adjuvant Radiation ◽  
Success Rates

Cutaneous squamous cell carcinoma of the head and neck is an epidemic that reaches all parts of the world. Making the diagnosis relies on the acumen of the clinician and pathologist. Various pathologic subtypes exist and differ in histology and prognosis. High-risk tumors need aggressive treatment and vigilant surveillance to monitor for recurrence. Large tumors, deep tissue invasion, perineural involvement, recurrence, location in high-risk areas, and immunosuppression are implicated in worsening prognosis. Surgery is the mainstay of treatment with adjuvant radiation therapy as needed for aggressive tumors; however, other modalities are potentially useful for low-risk lesions. The use of Mohs surgery has become increasingly useful and has shown high success rates. Involvement of parotid and neck lymph nodes significantly affects outcomes and the physician should be comfortable with management of this complex disease. This paper examines the diagnosis, pathology, clinical course, and treatment options for cutaneous squamous cell carcinoma of the head and neck.

scholarly journals Actual treatment options for locally advanced and metastatic cutaneous squamous cell carcinoma

2021 ◽  
Vol 23 (1) ◽  
pp. 94-98
Author(s):  
Anastasia V. Ignatova
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Locally Advanced ◽  
Cutaneous Squamous Cell Carcinoma ◽  
Molecular Profile ◽  
New Information ◽  
New Treatment

Squamous cell carcinoma of the skin, or cutaneous squamous cell carcinoma (CSCC), is the second most frequent type of skin cancer, and its incidence continues to rise all over the world. Usually has a benign clinical behavior, but it can be presented as locally invasive and metastatic aggressive tumor with 2% mortality rate. Nowadays, new risk factors for have appeared, that form pharmacologically-induced CSCC after immunosuppressant drugs used for organ transplantation, or BRAF inhibitors used for melanoma. In recent years we have got a new information about the role of mutational burden, signaling pathways involved in CSCC development and new possibilities and molecules for targeted therapy. Better understanding of the immune system functioning and benefits of immunotherapy with immune checkpoint inhibitors (PD-1) for CSCC that has changed the therapeutic approach. According to recent clinical trials data, new treatment options with PD-1 inhibitors achieved a response rate of 50% for locally advanced CSCC and 47% for metastatic CSCC, including 16.1% complete remissions. This review focuses on the molecular profile, targeted therapies and immunotherapy for locally advanced and metastatic CSCC.

scholarly journals CASE (CemiplimAb-rwlc Survivorship and Epidemiology) study in advanced cutaneous squamous cell carcinoma

2020 ◽  
Vol 16 (4) ◽  
pp. 11-19 ◽  
Author(s):  
Michael R Migden ◽  
Sunandana Chandra ◽  
Guilherme Rabinowits ◽  
Chieh-I Chen ◽  
Jigar Desai ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Real World ◽  
Locally Advanced ◽  
Cutaneous Squamous Cell Carcinoma ◽  
Epidemiology Study ◽  
Curative Surgery ◽  
Registration Number ◽  
Us Fda

In 2018, cemiplimab-rwlc became the first systemic treatment approved by the US FDA for patients with metastatic cutaneous squamous cell carcinoma (CSCC) or locally advanced CSCC who are not candidates for curative surgery or curative radiation. In 2019, conditional approvals were granted by Health Canada and the European Commission for the same indications. Limited data exist pertaining to the clinical characteristics, disease progression and survivorship of patients with advanced CSCC in real-world clinical practice. CemiplimAb-rwlc Survivorship and Epidemiology (CASE) is a prospective Phase IV, noninterventional, survivorship and epidemiology study that will enroll patients with advanced CSCC who have recently initiated or who plan to receive cemiplimab in a real-world setting. Trial registration number: NCT03836105.

scholarly journals Oncogenic ALKF1174L drives tumorigenesis in cutaneous squamous cell carcinoma

2020 ◽  
Vol 3 (6) ◽  
pp. e201900601
Author(s):  
Marco Gualandi ◽  
Maria Iorio ◽  
Olivia Engeler ◽  
André Serra-Roma ◽  
Giuseppe Gasparre ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Cutaneous Squamous Cell Carcinoma ◽  
Cell Of Origin ◽  
Anaplastic Lymphoma ◽  
Downstream Effector ◽  
Tumorigenic Potential ◽  
Common Skin ◽  
First Time

Cutaneous squamous cell carcinoma (cSCC) is the second most common skin cancer characterized by increased mortality. Here, we show for the first time that anaplastic lymphoma kinase (ALK), a receptor tyrosine kinase of the insulin receptor superfamily, plays a pivotal role in the pathogenesis of cSCC. Our data demonstrate that the overexpression of the constitutively active, mutated ALK, ALKF1174L, is sufficient to initiate the development of cSCC and is 100% penetrant. Moreover, we show that cSCC development upon ALKF1174L overexpression is independent of the cell-of-origin. Molecularly, our data demonstrate that ALKF1174L cooperates with oncogenic KrasG12D and loss of p53, well-established events in the biology of cSCC. This cooperation results in a more aggressive cSCC type associated with a higher grade histological morphology. Finally, we demonstrate that Stat3 is a key downstream effector of ALKF1174L and likely plays a role in ALKF1174L-driven cSCC tumorigenesis. In sum, these findings reveal that ALK can exert its tumorigenic potential via cooperation with multiple pathways crucial in the pathogenesis of cSCC. Finally, we show that human cSCCs contain mutations in the ALK gene. Taken together, our data identify ALK as a new key player in the pathogenesis of cSCC, and this knowledge suggests that oncogenic ALK signaling can be a target for future clinical trials.

scholarly journals Cutaneous Squamous Cell Carcinoma in Solid Organ Transplant Patients

2020 ◽  
Vol 78 (4) ◽  
pp. 245-351
Author(s):  
Leandro Silva ◽  
João Borges-Costa
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Treatment Options ◽  
Organ Transplant ◽  
Hpv Infection ◽  
Immunosuppressive Drugs ◽  
Solid Organ Transplant ◽  
Cutaneous Squamous Cell Carcinoma ◽  
Solid Organ

Solid organ transplant recipients (SOTR) are more likely to develop cutaneous squamous cell carcinoma (CSCC), compared to the general population. This increased incidence is due to several factors including chronic ultraviolet radiation exposure, human papillomavirus (HPV) infection, immunosuppressive medication, among others. Primary prevention is crucial, because not only are cutaneous squamous cell carcinomas more frequent in SOTR, but they are also more aggressive and have therefore a worse prognosis. Newer immunosuppressive drugs are associated with a smaller risk of developing CSCC, but they can have more adverse events, prompting patients to abandon therapy. Concerning treatment options for CSCC, they range from surgery, radiotherapy, and systemic therapy, although there are few studies in SOTR concerning the use of immunotherapy and epidermal growth factor receptor (EGFR) inhibitors.  

scholarly journals Multidisciplinary management of locally advanced and metastatic cutaneous squamous cell carcinoma

2020 ◽  
Vol 27 (4) ◽  
Author(s):  
J. Claveau ◽  
J. Archambault ◽  
D.S. Ernst ◽  
C. Giacomantonio ◽  
J.J. Limacher ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Treatment Options ◽  
Locally Advanced ◽  
Cutaneous Squamous Cell Carcinoma ◽  
Severe Toxicity ◽  
Curative Surgery ◽  
Skin Cancers ◽  
Clinical Benefits

Non-melanoma skin cancers are the most prevalent form of cancer, with cutaneous squamous cell carcinoma (cscc) being the 2nd most common type. Patients presenting with high-risk lesions associated with locally advanced or metastatic cscc face high rates of recurrence and mortality. Accurate staging and risk stratification for patients can be challenging because no system is universally accepted, and no Canadian guidelines currently exist.    Patients with advanced cscc are often deemed ineligible for either or both of curative surgery and radiation therapy (rt) and, until recently, were limited to off-label systemic cisplatin–fluorouracil or cetuximab therapy, which offers modest clinical benefits and potentially severe toxicity. A new systemic therapy, cemiplimab, has been approved for the treatment of locally advanced and metastatic cscc. In the present review, we provide recommendations for patient classification and staging based on current guidelines, direction for determining patient eligibility for surgery and rt, and an overview of the available systemic treatment options for advanced cscc and of the benefits of a multidisci­plinary approach to patient management.

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