Chromosome 3q arm gain linked to immunotherapy response in advanced cutaneous squamous cell carcinoma

Kacew, Alec; Harris, Ethan; Lorch, Jochen H.; Haddad, Robert I.; Chau, Nicole G.; Rabinowits, Guilherme; LeBoeuf, Nicole R.; Schmults, Chrysalyne D.; MacConaill, Laura E.; Hanna, Glenn J.

doi:10.1016/j.ejca.2019.03.004

Cited by 21 publications

(25 citation statements)

References 27 publications

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“… 36 Previously published sequencing data for immunotherapy-treated advanced cSCC patients of all ages from this institution (minimum age 52, n = 16; no overlap with the current cohort) 37 showed a median TMB of 33 muts/Mb (range: 4–137), which was higher compared to our older cSCC cohort (33 versus 11.8 muts/Mb, P = 0.03). Other sequencing reports have included aggressive primary cSCC and lymph node metastases (not CPI treated) showing similarly higher median TMB values (among all coding regions) >60 muts/Mb 30 , 38 , 39 in the absence of age restriction or mention of immunosuppression. We speculate that our results reflect a sampling bias, whereby 62% of sequenced cSCC cases were metastatic sites with biopsies obtained years after initial diagnosis and prior treatments; thus, TMB would be expected to be comparatively lower due to clonal selection and metastatic heterogeneity.…”

Section: Discussionmentioning

confidence: 97%

Real-world outcomes treating patients with advanced cutaneous squamous cell carcinoma with immune checkpoint inhibitors (CPI)

et al. 2020

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Background Immunotherapy has revolutionised the treatment of advanced cutaneous squamous cell carcinoma (cSCC). It is important to understand both safety and efficacy in a real-world and trial-ineligible cSCC population. We aimed to evaluate safety, efficacy and molecular insights among a broader cSCC population, including immunosuppressed patients, treated with immune checkpoint inhibitors (CPI). Methods We present a cohort of advanced cSCC patients (n = 61) treated from 2015 to 2020 evaluating the best overall response (BOR) (RECISTv1.1) to CPI therapy, immune-related adverse events (irAEs) and tumour mutational burden (TMB) to correlate with outcomes. A validated geriatric scoring index (CIRS-G) was utilised to assess comorbidities among patients ≥75. These data were compared with published clinical trial results among the broader cSCC population. Results BOR to CPI was lower among the entire cohort when compared with trial data (31.5 vs. 48%, P < 0.01), with higher rates of progression (59 vs. 16.5%, P < 0.01), regardless of immunosuppression history or age. Grade 3+ irAEs were more common among responders (P = 0.02), while pre-treatment lymphocyte count and TMB predicted response (P = 0.02). Conclusions We demonstrate comparatively lower response rates to CPI among real-world cSCC patients not explained by older age or immunosuppression history alone. Immune-related toxicity, absolute lymphocyte count and TMB predicted CPI response.

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Section: Discussionmentioning

confidence: 97%

Real-world outcomes treating patients with advanced cutaneous squamous cell carcinoma with immune checkpoint inhibitors (CPI)

et al. 2020

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“…Transplant patients represent a group in which the use of checkpoint inhibitors presents a problem because enhanced T-cell activation can lead to allograft rejection [106,133,134]. Limited data exist because transplant patients are often excluded from clinical trials, and only data from isolated cases are available [130,135,136].…”

Section: Immunotherapy In Csccmentioning

confidence: 99%

Cutaneous Squamous Cell Carcinoma: From Biology to Therapy

Corchado-Cobos

García-Sancha

González-Sarmiento

et al. 2020

IJMS

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Cutaneous squamous cell carcinoma (CSCC) is the second most frequent cancer in humans and its incidence continues to rise. Although CSCC usually display a benign clinical behavior, it can be both locally invasive and metastatic. The signaling pathways involved in CSCC development have given rise to targetable molecules in recent decades. In addition, the high mutational burden and increased risk of CSCC in patients under immunosuppression were part of the rationale for developing the immunotherapy for CSCC that has changed the therapeutic landscape. This review focuses on the molecular basis of CSCC and the current biology-based approaches of targeted therapies and immune checkpoint inhibitors. Another purpose of this review is to explore the landscape of drugs that may induce or contribute to the development of CSCC. Beginning with the pathogenetic basis of these drug-induced CSCCs, we move on to consider potential therapeutic opportunities for overcoming this adverse effect.

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“…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%

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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Chromosome 3q arm gain linked to immunotherapy response in advanced cutaneous squamous cell carcinoma

Cited by 21 publications

References 27 publications

Real-world outcomes treating patients with advanced cutaneous squamous cell carcinoma with immune checkpoint inhibitors (CPI)

Real-world outcomes treating patients with advanced cutaneous squamous cell carcinoma with immune checkpoint inhibitors (CPI)

Cutaneous Squamous Cell Carcinoma: From Biology to Therapy

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

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