PD-1 inhibition therapy for advanced cutaneous squamous cell carcinoma: a retrospective analysis from the University of Southern California

In, Gino K; Vaidya, Poorva; Filkins, Alexandra; Hermel, David J.; King, Kevin G.; Ragab, Omar; Tseng, William W.; Swanson, Mark S.; Kokot, Niels; Lang, Julie E.; Menendez, Lawrence R.; DeClerck, Brittney; Kim, Gene; Hu, Jenny; Terando, Alicia M.; Jadvar, Hossein; Ricker, Charité; Miller, Kimberly A.; Peng, David H.; Wysong, Ashley

doi:10.1007/s00432-020-03458-6

Cited by 25 publications

(50 citation statements)

References 39 publications

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“…What is worthy of consideration is that, compared to controlled clinical trials (17,30) and other real-world series (20-24), our CSCC cohort has been less pretreated even with radiotherapy and surgery. Furthermore, accordingly with other authors, we observed a higher response rate associated with fewer surgical procedures (17) and for CSCC arising in the head and neck area (20)(21)(22)(23). This last finding could reflect the influence of a higher degree of sun exposure on the mutational burden notoriously associated with a better response to immuno-checkpoint inhibitors (21,22).…”

Section: Discussionsupporting

confidence: 88%

“…We observed an unexpected overall response rate of 76% with complete responses of 30%. Despite the poor profile of our patients, these results are better than those reported in controlled trials and initial real-world series showing 31 to 58% overall responses, respectively (14,(20)(21)(22)(23)(24). Our better results could likely be due to the prevalence of locally advanced over metastatic stage in our patient population and to the use of cemiplimab as first-line therapy in the majority of patients, which is notoriously associated to better response (34).…”

Section: Discussioncontrasting

confidence: 53%

“…In our observational study, we reported a population with a median age of 81 years, which is higher than that reported in controlled clinical trials (71 and 74 years in mCSCC and laCSCC, respectively) and in other real-world experiences (20)(21)(22)(23)(24), and a prevalence of frailty of 83%, which is greater than that reported in a metanalysis in generalized (18) and specific oncologic settings (19). Although there is no standard instrument to identify frailty, we set up a frail index based on a simple scoring system that accounts the main tool to assess vulnerability such as age, performance status, and comorbidity.…”

Section: Discussionmentioning

confidence: 66%

“…These clinical features are often found in the real-world population of advanced CSCC and collectively define frailty as a common vulnerability condition among older cancer patients which is associated to an increased risk for poor therapeutic outcomes (18,19). Thus, due to the limited data still available in non-selected patients (14,(20)(21)(22)(23)(24), in this paper, we report our experience with cemiplimab in a frail population treated outside controlled clinical trials and including very elderly patients presenting with several co-morbidities and patients with immunosuppressive conditions requiring a careful assessment of the cost-benefit profile of treatment. Moreover, owing to the absence of biomarkers able to predict response that would guide the therapeutic choice, we investigated the correlations between therapy outcomes and both clinical and blood parameters.…”

Section: Introductionmentioning

confidence: 99%

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Cemiplimab in an Elderly Frail Population of Patients With Locally Advanced or Metastatic Cutaneous Squamous Cell Carcinoma: A Single-Center Real-Life Experience From Italy

et al. 2021

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BackgroundCutaneous squamous cell carcinoma (CSCC) is the second most common skin cancer whose incidence is growing parallel to the lengthening of the average lifespan. Cemiplimab, an antiPD-1 monoclonal antibody, is the first approved immunotherapy for patients with locally advanced CSCC (laCSCC) or metastatic CSCC (mCSCC) thanks to phase I and II studies showing high antitumor activity and good tolerability. Nevertheless, at present, very few data are available regarding cemiplimab in real-life experience and in frail, elderly, and immunosuppressed patients as well as regarding biomarkers able to predict response so as to guide therapeutic choices.Patients and MethodsWe built a retroprospective cohort study including 30 non-selected patients with laCSCC (25) and mCSCC (five) treated with cemiplimab from August 2019 to November 2020. Clinical outcomes, toxicity profile, and correlations with disease, patients, and peripheral blood parameters are explored.ResultsThe median age was 81 years (range, 36–95), with 24 males and five patients having an immunosuppressive condition, while the frailty prevalence was 83% based on index derived from age, Eastern Cooperative Oncology Group performance status, and Charlson Comorbidity Index. We reported 23 responses (76.7%) with nine complete responses (30%). A statistically significant higher response rate was observed in head and neck primary tumors and in patients with hemoglobin level >12 g/dl. No difference was observed with respect to frailty, median age, sex, and body mass index. The baseline low neuthophil/lymphocyte ratio and low platelet/lymphocyte ratio resulted to be also correlated with a better response. Moreover, lymphocyte, neutrophil, and monocyte behaviors had an opposite trend in responders and non-responders. An overall response was reported in four of five immunosuppressed patients. Seventeen patients (57.6%) have an ongoing response and are still alive. Six responders had interrupted treatment (two for toxicity and four for personal choice) but maintained their response. The treatment was well tolerated by the majority of patients. The most common adverse events were fatigue in seven patients (23.3%) and skin toxicity in 10 patients (33.3%), including pruritus in six patients, rash in three patients, and bullous erythema in one patient.ConclusionsIn our real-life experience, cemiplimab showed a high antitumor activity with acceptable safety profile similar to those in trials with selected patients. Moreover, its antitumor activity resulted to be not impaired in very elderly patients and in those with immunocompromised status.

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Section: Discussionsupporting

confidence: 88%

Section: Discussioncontrasting

confidence: 53%

Section: Discussionmentioning

confidence: 66%

Section: Introductionmentioning

confidence: 99%

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Cemiplimab in an Elderly Frail Population of Patients With Locally Advanced or Metastatic Cutaneous Squamous Cell Carcinoma: A Single-Center Real-Life Experience From Italy

et al. 2021

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“…Immune checkpoints-based therapies are of great relevance especially for patients with advanced and metastatic disease that are not ideal candidates for surgical excision. A retrospective analysis showed that PD-1 inhibition produces durable responses among patients with advanced or metastatic SCC ( In et al, 2020 ). In a multicenter study, the overall response rate obtained among patients with advanced SCC was even higher ( Salzmann et al, 2020 ).…”

Section: Evasion Of the Immune Response: Potential Targets For Immunomentioning

confidence: 99%

The Tumor Microenvironment in SCC: Mechanisms and Therapeutic Opportunities

Amôr

Santos

Campanelli

2021

Front. Cell Dev. Biol.

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Squamous cell carcinoma (SCC) is the second most common skin cancer worldwide and, despite the relatively easy visualization of the tumor in the clinic, a sizeable number of SCC patients are diagnosed at advanced stages with local invasion and distant metastatic lesions. In the last decade, immunotherapy has emerged as the fourth pillar in cancer therapy via the targeting of immune checkpoint molecules such as programmed cell-death protein-1 (PD-1), programmed cell death ligand-1 (PD-L1), and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4). FDA-approved monoclonal antibodies directed against these immune targets have provide survival benefit in a growing list of cancer types. Currently, there are two immunotherapy drugs available for cutaneous SCC: cemiplimab and pembrolizumab; both monoclonal antibodies (mAb) that block PD-1 thereby promoting T-cell activation and/or function. However, the success rate of these checkpoint inhibitors currently remains around 50%, which means that half of the patients with advanced SCC experience no benefit from this treatment. This review will highlight the mechanisms by which the immune checkpoint molecules regulate the tumor microenvironment (TME), as well as the ongoing clinical trials that are employing single or combinatory therapeutic approaches for SCC immunotherapy. We also discuss the regulation of additional pathways that might promote superior therapeutic efficacy, and consequently provide increased survival for those patients that do not benefit from the current checkpoint inhibitor therapies.

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Risk factors and novel predictive model for metastatic cutaneous squamous cell carcinoma: a population-based analysis

Zhang

Liu

et al. 2023

Arch Dermatol Res

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PD-1 inhibition therapy for advanced cutaneous squamous cell carcinoma: a retrospective analysis from the University of Southern California

Cited by 25 publications

References 39 publications

Cemiplimab in an Elderly Frail Population of Patients With Locally Advanced or Metastatic Cutaneous Squamous Cell Carcinoma: A Single-Center Real-Life Experience From Italy

Cemiplimab in an Elderly Frail Population of Patients With Locally Advanced or Metastatic Cutaneous Squamous Cell Carcinoma: A Single-Center Real-Life Experience From Italy

The Tumor Microenvironment in SCC: Mechanisms and Therapeutic Opportunities

Risk factors and novel predictive model for metastatic cutaneous squamous cell carcinoma: a population-based analysis

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