Long-term survival after anti-PD-1 discontinuation in advanced cutaneous squamous cell carcinoma (cSCC): a proof of concept of benefit of concomitant cemiplimab and radiotherapy.

BACKGROUND: In a princeps study we conducted in patients with advanced cutaneous squamous cell carcinoma treated with concomitant anti-Programmed cell death protein 1 (PD-1) and radiotherapy, we demonstrated a clinico radiological response to cemiplimab that appeared to persist over time, 1 year after treatment discontinuation. METHOD: We conducted a single-center descriptive study at Caen Hospital from September 1, 2021 to September 2023, in 14 patients with advanced carcinoma treated with cemiplimab until September 1, 2021. The aim of this update is to examine clinical and radiological follow-up 2 years after discontinuation of cemiplimab. RESULTS: Of the 12 patients with a partial or complete response, we report 8 (66.7%) persistent responses 2 years after stopping cemiplimab, with only 2 patients progressing to distant disease, one lost to follow-up, and one death a priori unrelated to the disease. CONCLUSION: Our study confirms a long-term and persistent effect despite discontinuation of cemiplimab at least up to 2 years later.

Impact of cemiplimab treatment duration on clinical outcomes in advanced cutaneous squamous cell carcinoma.

Treatment duration with checkpoint inhibitors must be optimized to prevent unjustified toxicity, but evidence for the management of cutaneous squamous cell carcinoma is lacking. A retrospective study was performed to evaluate the survival of patients with cutaneous squamous cell carcinoma (CSCC) who discontinued cemiplimab due to different causes and without progression. Among 95 patients with CSCC who received cemiplimab, 22 (23%) patients discontinued immunotherapy due to causes other than progression, such as comorbidities, toxicity, complete response or lack of compliance (group that discontinued before censoring [DBC]), then 73 patients had standard treatment scheduled (STS). The overall survival was 25.2 months (95% CI: 8.9-29.4) in STS group and 28.3 months (95% CI: 12.7-28.3) in the DBC group; deaths for all causes were 11/22 (50%) in the DBC group and 34/73 (46.6%) in the STS group (p = 0.32). 10/22 (45.4%) subjects died due to CSCC in the DBC after discontinuation and 34/73 (46.6%) in the STS group, and the difference between groups was not significant (p = 0.230). Duration of treatment was significantly lower in subjects with stable disease versus those with complete or partial response (16.9, 30.6 and 34.9 months, respectively; p = 0.004). Among the 22 STS patients, 12 received cemiplimab for less than 12 months (10 [83%] died) and 10 for at least 12 months (1 [10%] died). Our observation, finding no outcome difference between DBC and STS groups, suggests that ICI treatment after one year might expose patients to further treatment related events without efficacy advantages.

Economic evaluation of cemiplimab plus chemotherapy regimen for advanced non-small-cell lung cancer.

OBJECTIVE: Cemiplimab, a novel PD-1 inhibitor, exhibits significant antitumor activity against advanced non-small cell lung cancer (NSCLC). However, the cost-effectiveness of this drug for the treatment remains unclear. This study aimed to assess the cost-effectiveness of cemiplimab plus chemotherapy compared to chemotherapy for the treatment of advanced NSCLC, from the perspective of the United States payer. METHODS: A partitioned survival approach was developed to project the disease progression of NSCLC. Overall survival (OS) and progression-free survival (PFS) data were obtained from the EMPOWER lung 3 trial and extrapolated to estimate long-term survival outcomes. Direct medical costs and utility data were collected. The primary outcome measure, the incremental cost-utility ratio (ICUR), was used to evaluate the cost-effectiveness of cemiplimab plus chemotherapy regimen. One-way sensitivity analyses (OWSA) and probabilistic sensitivity analyses (PSA) were conducted to assess the robustness of the results. RESULTS: In the base-case analysis, the ICUR for cemiplimab plus chemotherapy versus chemotherapy alone was estimated to be $395,593.8 per quality-adjusted life year (QALY). OWSA revealed that the results were sensitive to Hazard ratio value, utility of PFS, and cost of cemiplimab. PSA demonstrated that cemiplimab plus chemotherapy exhibited 0% probability of cost-effectiveness.In hypothetical scenario analysis, the ICUR of two regimens was $188.803.3/QALY. OWSA revealed that the results were sensitive to the discount rate, utility, and cost of cemiplimab. PSA indicated that cemiplimab plus chemotherapy achieved at least an 11.5% probability of cost-effectiveness. CONCLUSION: Our cost-effectiveness analysis suggests that, at its current price, cemiplimab plus chemotherapy regimen is unlikely to be a cost-effective option compared with chemotherapy alone for advanced NSCLC patients, based on a threshold of $150,000 per QALY, from the perspective of the US payer.

Previous radiotherapy increases the efficacy of cemiplimab in the treatment of locally advanced and metastatic cutaneous squamous cell carcinoma: A retrospective analysis.

BACKGROUND: Cemiplimab, a programmed cell death-1 inhibitor approved in 2018 for patients with locally advanced or metastatic cutaneous squamous cell carcinoma (cSCC) who are ineligible for curative therapies, lacks clarity regarding the optimal patient selection despite its known efficacy. OBJECTIVE: This retrospective study aims to assess the real-world treatment patterns and outcomes in patients with cSCC at our institution. METHODS: A retrospective analysis of consecutively treated patients with cemiplimab for cSCC was conducted. Progression-free survival (PFS) and overall survival were evaluated alongside clinical-pathologic characteristics. RESULTS: Forty-five patients were included, of which 73.3% were male with a median age of 77 years. After 18 months of median follow-up median PFS and overall survival were not reached with a mean of 21.3 months ± 2.2 months and 25.3 ± 2.1 months, respectively. Univariate and multivariate analyses revealed significant correlations only between PFS and previous radiotherapy (P values: .043 and .046, respectively). LIMITATIONS: Limitations include its retrospective nature, the low number of patients analyzed, and the potential for inherent biases. CONCLUSIONS: The study reveals a significant association between prior radiotherapy and improved PFS in cemiplimab-treated cSCC, suggesting the potential for combining radiotherapy with cemiplimab. Further exploration of this combined approach is warranted.

Quality of life in cemiplimab-treated patients with locally advanced basal cell carcinoma in a Phase II clinical trial.

Aim: To evaluate health-related quality of life (HRQoL) in cemiplimab-treated patients with locally advanced basal cell carcinoma (laBCC).Materials & methods: Eighty-four patients with laBCC received cemiplimab 350 mg every 3 weeks (up to 9 cycles). HRQoL was assessed using the European Organization for Research and Treatment of Cancer Quality of Life Core 30 (QLQ-C30) and Skindex-16 questionnaires at baseline and each cycle. Mixed-effects repeated-measures models evaluated change from baseline across cycles.Results: Clinically meaningful improvement or maintenance was reported by 62-90% of patients on QLQ-C30 scales and by approximately 80% on Skindex-16 scales at Cycle 2, with consistent results at Cycle 9 except fatigue.Conclusion: Most cemiplimab-treated patients with laBCC reported improvement or maintenance of HRQoL with low symptom burden except fatigue.Clinical Trial Registration: ClinicalTrials.gov identifier NCT03132636, registered 28 April 2017.

Locally advanced basal cell carcinoma (laBCC) is a type of skin cancer that has the potential to invade surrounding tissues including bone, cartilage, nerve and muscle. Cemiplimab-rwlc is approved in the US for patients with laBCC following a therapy called hedgehog inhibitor (HHI) treatment or for whom HHIs are not appropriate. In a Phase II clinical trial, intravenous (in the vein) cemiplimab 350 mg every 3 weeks for up to nine treatment cycles resulted in clinically meaningful antitumor activity in patients with laBCC who progressed on or were intolerant to HHIs.This analysis evaluated health-related quality of life, symptom burden, emotions and functional status in these patients using the European Organization for Research and Treatment of Cancer Quality of Life Core 30 (QLQ-C30) and Skindex-16 questionnaires. Baseline scores (scores at the start of the clinical trial) showed moderate to high levels of functioning and low symptom burden that, except for fatigue, were maintained or improved over the course of cemiplimab treatment. These results show that despite the presence of fatigue, health-related quality of life and functional status were maintained with cemiplimab across the study duration.

Acute kidney injury associated with anti-PD-1 and anti-PD-L1 drugs: a meta-analysis of randomized clinical trials.

BACKGROUND: Immune Checkpoint Inhibitors (ICI) have been widely used in treating different types of cancer. They increase survival in many oncologic patients and enable cancer-specific therapy. Acute Kidney Injury (AKI) is one of the adverse effects associated with using ICI, where knowledge of the prevalence and renal histological findings are still reasons for discussion. OBJECTIVE: Therefore, this meta-analysis evaluates the association between ICI use and AKI. METHODS: The search was performed in PubMed, Lilacs, and Cochrane platforms. Studies published up to December 1, 2022, were included. RESULTS: A total of 16 studies met the established PICOT criteria and were included in this review. Comparing the ICI plus chemotherapy against chemotherapy alone, the relative risk (RR) for AKI's development with ICI use was 2.89 (95%CI 1.37-6.10). In the analyses by class and drug type, programmed cell death 1 monoclonal antibody (anti-PD-1) showed an increased risk of 2.11 (95%CI 1.26-3.52), and pembrolizumab demonstrated a risk of AKI (RR= 2.77, 95%CI 1.46-5.26). Likewise, regarding the severity of AKI, AKI grade 3 or higher was more common in the ICI plus chemotherapy compared to the chemotherapy group: 3.66 (95%CI 1.19-11.30), while the subgroup analyses pooled studies comparing ICI alone versus chemotherapy alone in the control group did not demonstrate an association with AKI. CONCLUSIONS: These findings suggest that ICI use is associated with an increased risk of AKI and that anti-PD-1 use is associated with a higher incidence of renal adverse events than programmed cell death ligand 1 monoclonal antibody (anti-PD-L1). Studies with adequate power and well-defined criteria for acute interstitial nephritis, nowadays taken as a synonym for AKI related to ICI, are necessary.

Advanced cutaneous squamous cell carcinoma: Impact of age on the safety and efficacy of cemiplimab and the prognostic significance of blood biomarkers.

INTRODUCTION: Age-related differences in the safety profile of cemiplimab for patients with locally advanced or metastatic cutaneous squamous cell carcinoma (cSCC) have not been well described. We investigated the association of increasing age with immune related adverse events (irAE) from cemiplimab, efficacy outcomes, and the prognostic significance of pre-treatment blood biomarkers in contemporary practice. MATERIALS AND METHODS: Patients starting first-line cemiplimab for locally advanced or metastatic cSCC at British Columbia Cancer between April 2019 and January 2023 were identified. Landmark four-month logistic regression analysis compared the odds of developing irAE or sequelae amongst patients aged <75 years to those aged 75-84 or ≥ 85. Objective responses were determined using Response Evaluation Criteria in Solid Tumors version 1.1. Univariable Cox proportional hazard (PH) regression modelling of factors associated with overall survival (OS) was performed. RESULTS: Of 106 patients, the proportions aged <75, 75-84, and ≥ 85 years were 34%, 45%, and 21%, respectively. Overall, the proportion of patients with irAE ≥ grade 3, cemiplimab discontinuation, and hospitalization for immune toxicity was 27.4%, 31.1%, and 11.3%, respectively. There was no clear association between age and the odds of high grade irAE. However, increased odds of cemiplimab discontinuation was observed in patients aged 75-84 years (p = 0.05). Patients ≥85 years had increased hospitalizations due to irAE (OR = 5.00, 95% CI = 0.97-37.52) with two treatment-related deaths. Objective responses were similar across age cohorts (50.0%, 60.4%, and 54.5%) but progressive disease was higher in the age ≥ 85 group (22.2%, 18.8%, and 31.8%). On Cox PH regression analysis, age ≥ 85 years (vs. <75), Eastern Cooperative Oncology Group performance status 2-3 (vs. 0-1), and neutrophil to lymphocyte ratio (NLR) ≥7.80 (vs. <7.80) were associated with shorter survival. DISCUSSION: While the odds of high grade irAE were similar across age groups, significant age-related differences in treatment discontinuation and hospitalization due to immune toxicity were observed. Despite a higher incidence of primary progression and shorter OS in the oldest cohort, cemiplimab yielded robust objective responses regardless of age. Higher pre-treatment NLR was associated with shorter survival and the cut-point identified requires further study.

The Immunomodulatory Potential of Concurrent High-Dose Radiotherapy and Immune Checkpoint Inhibitor Cemiplimab in Advanced Cutaneous Squamous Cell Carcinoma: Initial Results.

In this retrospective case series, we investigate the synergistic effect and the immunomodulatory potential of combination radiotherapy and immunotherapy on 11 patients affected by locally advanced or metastatic cutaneous squamous cell carcinoma (CSCC), treated at our institution between 2020 and 2023. The primary endpoints of this study are objective tumor response, assessed by Immunotherapy Response Evaluation Criteria in Solid Tumors (iRECIST), and time to treatment failure (disease progression). In all patients, surgery was deemed not amenable, due to its potential functional and aesthetic impact. Therefore, upon multidisciplinary agreement, radiotherapy and immunotherapy with cemiplimab were alternatively administered. After 6 months, an early objective tumor response was observed in 9/11 patients, with 17/20 cutaneous lesions (85%) presenting either a complete or partial response. Only 2/11 patients, with a total of 3/20 cutaneous lesions (15%), had stable disease. These benefits persisted at a longer follow-up (21.4 ± 9.7 months), with no patients presenting disease progression. Despite the retrospective nature of this study and small sample size, our experience highlights the ability of concomitant radiotherapy and cemiplimab to promote an early objective response in patients with advanced CSCC. Moreover, in our population, the clinical benefits were also related to a longer progression-free survival, without any safety alert reported.

Real-life efficacy and safety of cemiplimab in advanced cervical cancer from a nominal use program in Italy: The MITO 44 study.

BACKGROUND: cemiplimab is an immunoglobulin G4 monoclonal antibody targeting the programmed cell death-1 receptor. A nominal use program is available in Italy in advanced cervical cancer (CC) patients treated with platinum based chemotherapy based on the results of EMPOWER-Cervical 1/GOG-3016/ENGOTcx9 trial. This real-world, retrospective cohort, multicenter study aimed at describing clinical outcomes of patients with advanced CC treated with cemiplimab in Italy. METHODS: The primary objective of the study was to assess the feasibility and the replicability of the initial results in a real world setting of cemiplimab nominal use. The primary endpoint of our analysis was progression free survival (PFS). Secondary endpoints included overall response rate (ORR), overall survival (OS) and safety data. RESULTS: From March 2022 to December 2023, 135 patients were treated in 12 Multicenter Italian Trials in Ovarian cancer and gynecologic malignancies (MITO) Centers. Forty-two percent of patients had one or more comorbidities, hypertension being the most common (23.4%). Median PFS was 4.0 months (range 3.0-6.0) and median OS was 12.0 months (12.0- NR) with no differences according to PD-L1 status. Complete response (CR) or no evidence of disease (NED) were observed in 8.6%; partial response (PR) in 21.1%, stable disease (SD) in 14.8% and progression was recorded in 44.5% of patients. Most common drug related adverse events (AEs) were anemia (39.1%) and fatigue (27.8%). Immune related AEs occurred in 18.0%. CONCLUSIONS: This study confirms the feasibility and the replicability of the cemiplimab nominal use in advanced CC, in a real-world practice in Italy.

Clinical Outcomes and Prognostic Factors in Patients With Penile Carcinoma: A Sub-Analysis From Meet-URO 23 (I-RARE) Registry Study.

INTRODUCTION: Penile squamous cell carcinoma (PSCC) is a rare tumor with an aggressive behavior. The Meet-URO 23/I-RARE registry includes rare genitourinary malignancies. We extracted patients with PSCC to conduct a retrospective study aimed at assessing clinical outcomes and prognostic factors. PATIENTS AND METHODS: Primary endpoints were overall survival and progression-free survival. Prognostic factors for OS and PFS were analyzed using univariate and multivariate analysis. From the Meet-URO 23/I-RARE database, we extracted 128 patients with diagnosis of PSCC. About 48% of patients underwent first-line of therapy. RESULTS: In the overall population, median OS from diagnosis was 34.6 months. Significant differences in median OS were observed according to ECOG PS at diagnosis (57.3 months vs. 8.3 months; P < .001), and median age (≤77y 88.8 months vs. >77y 26 months; P = .013). At multivariate analysis, ECOG PS 2-4 at diagnosis (HR 3.04) and lymph node metastases (HR 2.49) were independently associated with a higher risk of death. Among patients undergoing first-line therapy (n = 61), median OS was 12.3 months, and a statistically significant difference was found according to type of response to first-line (DCR 24.4 months vs. PD 7.1 months; P < .001). Multivariate analysis showed that only age >77 years was associated with a worse OS (HR 2.16). A statistically significant difference in PFS was found according to platinum plus 5-fluorouracil versus platinum plus taxane (4.9 vs. 3.4 months; P = .036) and regimens with 2 versus 3 drugs (3.4 vs. 8.6 months; P = .019). At the multivariate analysis only regimens with platinum plus taxane were associated with worse PFS (HR 2.83). CONCLUSION: In our registry study, PSCC is confirmed to be an aggressive disease. Poor ECOG PS, presence of lymph node metastases, and higher age at diagnosis appear to be associated with worse survival outcomes.

Real-world evidence study on the early use of cemiplimab in the UK: REACT-CEMI (Real World evidence of advanced CSCC treatment with cemiplimab).

Background: Cemiplimab was licensed in the United Kingdom (UK) in 2019 for the treatment of patients with locally advanced and metastatic CSCC not suitable for curative surgery or radiotherapy (advanced CSCC [aCSCC]). No UK multi-center studies have investigated the real-world experience of cemiplimab post marketing authorization in aCSCC. Methods: This non-interventional retrospective study (10 UK centers) involved data collection from medical records of patients with aCSCC who initiated cemiplimab treatment between 2 July 2019 and 30 November 2020. The study period was a minimum of 12 and a maximum of 36 months post cemiplimab initiation. The primary objective was to describe the real-world clinical effectiveness of cemiplimab (primary outcome: overall response rate [ORR]). Results: Of 105 patients, 70% (n=73/105) were male (median [range] age at index of 78.5 [55.4-93.2] years); most patients (63% [n=50/80]) had an Eastern Cooperative Oncology Group (ECOG) score of 1 and 62% (n=63/102) had metastatic disease. The ORR within 12 months was 42% (95% confidence interval [CI] 32%-51%) and the disease control rate was 62% (n=65/105). The median (95% CI) real-world progression-free survival and overall survival from index was 8.6 (6.0-18.7) and 21.0 (14.7-25.2) months, respectively. The median (range) number of cemiplimab infusions was 11.0 (1.0-44.0). Eighty-seven percent experienced no cemiplimab treatment interruptions; 13% (n=14/105) interrupted treatment due to immune-related adverse reactions (irARs) (47% [n=9/19] of treatment interruption events). Eighty-five percent (n=89/105) of patients had discontinued cemiplimab treatment by the end of the study; where reasons for discontinuation were recorded, 20% (n=17/87) discontinued due to the completion of their 2-year treatment course. Nineteen percent (n=20/105) of patients experienced irARs. Conclusion: Effectiveness and safety data in this study are broadly similar to previous real-world studies of cemiplimab and the EMPOWER-CSCC1 clinical trial; with our cohort representing a broader population (included immunocompromised and transplant patients). Results support the use of cemiplimab for the treatment of aCSCC in a real-world setting.

Multidisciplinary Management of Cutaneous Squamous Cell Carcinoma of the Scalp: An Algorithm for Reconstruction and Treatment.

Background: Scalp-associated cutaneous squamous cell carcinoma (cSCC) presents formidable treatment challenges, especially when it leads to full-thickness defects involving bone. Aggressive or recurring cases often demand a multidisciplinary approach. Leveraging our surgical experience and a literature review, we introduce a therapeutic algorithm to guide the selection of reconstruction methods, particularly for locally advanced lesions, furthermore showing the synergy between surgery and other therapies for comprehensive, multidisciplinary disease management. Methods: Our algorithm stems from a retrospective analysis of 202 patients undergoing scalp cSCC resection and reconstruction over a 7-year period, encompassing 243 malignancies. After rigorous risk assessment and documentation of surgical procedures, reconstruction methods were therefore related to malignancy extent, depth, and individual clinical status. Results: The documented reconstructions included 76 primary closures, 115 skin grafts, 7 dermal substitute reconstructions, 33 local flaps, 1 locoregional flap, and 1 microsurgical free flap. Patients unsuitable for surgery received radiotherapy or immunotherapy after histological confirmation. Precise analysis of tumor characteristics in terms of infiltration extent and depth guided the selection of appropriate reconstruction and treatment strategies Combining these insights with an extensive literature review enabled us to formulate our algorithm for managing scalp cSCCs. Conclusions: Effectively addressing scalp cSCC, especially in locally advanced or recurrent cases, demands a systematic approach integrating surgery, radiotherapy, and immunotherapy. Our multidisciplinary team's decision-making algorithm improved patient outcomes by offering a broader spectrum of therapeutic options that can synergistically achieve optimal results.

Cemiplimab in locally advanced or metastatic cutaneous squamous cell carcinoma: prospective real-world data from the DRUG Access Protocol.

Background: The DRUG Access Protocol provides patients with cancer access to registered anti-cancer drugs that are awaiting reimbursement in the Netherlands and simultaneously collects prospective real-world data (RWD). Here, we present RWD from PD-1 blocker cemiplimab in patients with locally advanced or metastatic cutaneous squamous cell carcinoma (laCSCC; mCSCC). Methods: Patients with laCSCC or mCSCC received cemiplimab 350 mg fixed dose every three weeks. Primary endpoints were objective clinical benefit rate (CBR), defined as objective response (OR) or stable disease (SD) at 16 weeks, physician-assessed CBR, defined as clinician's documentation of improved disease or SD based on evaluation of all available clinical parameters at 16 weeks, objective response rate (ORR), and safety, defined as grade ≥ 3 treatment related adverse events (TRAEs) occurring up to 30 days after last drug administration. Secondary endpoints included duration of response (DoR), progression-free survival (PFS), and overall survival (OS). Findings: Between February 2021 and December 2022, 151 patients started treatment. Objective and physician-assessed CBR were 54.3% (95% CI, 46.0-62.4) and 59.6% (95% CI, 51.3-67.5), respectively. ORR was 35.1% (95% CI, 27.5-43.3). After a median follow-up of 15.2 months, median DoR was not reached. Median PFS and OS were 12.2 (95% CI, 7.0-not reached) and 24.2 months (95% CI, 18.8-not reached), respectively. Sixty-eight TRAEs occurred in 29.8% of patients. Most commonly reported TRAE was a kidney transplant rejection (9.5%). Interpretation: Cemiplimab proved highly effective and safe in this real-world cohort of patients with laCSCC or mCSCC, confirming its therapeutic value in the treatment of advanced CSCC in daily clinical practice. Funding: The DRUG Access Protocol is supported by all participating pharmaceutical companies: Bayer, Janssen, Lilly, Merck, Novartis, Roche, and Sanofi.

Efficacy and Safety of Cemiplimab for the Management of Non-Melanoma Skin Cancer: A Drug Safety Evaluation.

Non-melanoma skin cancer includes several types of cutaneous tumors, with basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC) as the commonest. Among the available therapeutic options, surgical excision is the mainstay of treatment for both tumors. However, tumor features and patients' comorbidities may limit the use of these techniques, making the treatment challenging. As regards BCC, even if hedgehog inhibitors revolutionized the therapeutic scenario, there are still patients unresponsive or intolerant to these drugs. In this context, cemiplimab has been approved as second-line treatment. As regards SCC, cemiplimab was the first systemic therapy approved. The objective of this manuscript was to investigate the efficacy and safety of cemiplimab for the management of BCC and cSCC. Cemiplimab has a durable and significant effect for the management of BCC and CSCC, with a favorable safety profile. Different specialists including oncologists, radiologists, dermatologists, and surgeons are required to guarantee an integrated approach, leading to the best management of patients. Moreover, the collaboration among specialists will allow them to best manage the TEAEs, reducing the risk of treatment suspension or discontinuation. Certainly, ongoing studies and more and more emerging real-world evidence, will allow us to better characterize the role of cemiplimab for the management of advanced non-melanoma skin cancer.

A Retrospective Study of Cemiplimab Effectiveness in Elderly Patients with Squamous Cell Carcinoma of the Skin: Insights from a Real-Life Scenario.

INTRODUCTION: This retrospective study investigates the efficacy of cemiplimab, a monoclonal antibody targeting the PD-1 receptor, in treating squamous cell carcinoma (SCC) of the skin. METHODS: The study analyzes data from 50 patients with SCC, focusing on various clinical parameters, including patient demographics, tumor characteristics, treatment history, disease status at the beginning of therapy, and survival outcomes. RESULTS: Of the patients who received at least one cycle of cemiplimab, 42% showed a clinical response. Adverse reactions were generally low, with the safety profile deemed excellent. During a median follow-up of 9.6 months, 17 patients experienced progression or death. Among these, 15 patients had died at the time of the analysis. The median progression-free survival (PFS) for the entire cohort was approximately 20.8 months, while median overall survival (OS) was not reached. Univariate Cox regression analysis for PFS showed that tumors in the arms and legs were associated with higher progression risk, while age above 65 years was not statistically significant. Distant metastasis exhibited a trend towards improved PFS. In terms of OS, distant metastasis was a significant predictor of reduced survival, while age above 65 years was not statistically significant. In a multivariate model, only the absence of distant metastasis remained significant, with an adjusted odds ratio (OR) of 12.3 (95% confidence interval 1.3-112.1). CONCLUSION: These findings provide valuable insights into the real-world effectiveness of cemiplimab in SCC management.

Cemiplimab-Induced Hyperosmolar Hyperglycemic State With Concurrent Diabetic Ketoacidosis in a Patient Receiving Treatment for Cutaneous Squamous Cell Carcinoma.

The immune checkpoint inhibitor (ICI) cemiplimab is a human monoclonal antibody used in the treatment of locally advanced and metastatic cutaneous squamous cell carcinoma (CSCC) not amenable to surgery or radiation therapy. Although cemiplimab shows excellent efficacy with a good tolerability profile, it can cause side effects, including potentially life-threatening endocrinopathies. We discuss the case of a 77-year-old Caucasian female with CSCC treated with only three cycles of cemiplimab who presented with altered mental status and was found to have severe hyperglycemia, hyperosmolarity, ketonemia, glucosuria, and ketonuria concerning for hyperosmolar hyperglycemic syndrome (HHS) with concurrent diabetic ketoacidosis (DKA). The patient made a rapid recovery in the hospital while on standard therapies for HHS/DKA and cemiplimab was discontinued upon discharge. While there have been reports of cemiplimab-induced DKA, to our knowledge, this is the first reported case of cemiplimab-induced HHS-DKA. This report aims to shed light on cemiplimab-induced HHS-DKA and to underscore the need to elucidate the molecular mechanisms underlying ICI-induced diabetes mellitus (ICI-DM).

Cemiplimab plus chemotherapy versus chemotherapy alone in non-small cell lung cancer with PD-L1 ≥ 1 %: A subgroup analysis from the EMPOWER-Lung 3 part 2 trial.

OBJECTIVES: EMPOWER-Lung 3 part 2 (NCT03409614), a double-blind, placebo-controlled phase 3 study, assessed cemiplimab (anti-programmed cell death protein 1) plus chemotherapy versus chemotherapy alone in patients with advanced non-small cell lung cancer (NSCLC) without EGFR, ALK, or ROS1 aberrations, regardless of histology or PD-L1 expression levels. We report results from subgroup analysis of patients with PD-L1 expression ≥ 1 %. MATERIALS AND METHODS: Patients were randomized to receive cemiplimab 350 mg or placebo with chemotherapy every 3 weeks for up to 108 weeks. Overall survival (OS), progression-free survival (PFS), overall response rates (ORRs), patient-reported outcomes (PROs), and safety were assessed. RESULTS: Of the 327 patients with PD-L1 ≥ 1 % (466 in the overall study), 217 received cemiplimab plus chemotherapy and 110 received chemotherapy alone. After median follow-up of 28.0 months, median OS for cemiplimab plus chemotherapy was 23.5 months (95 % confidence interval [CI]: 20.9-27.2) vs. 12.1 months (95 % CI: 10.1-15.7) for chemotherapy alone (hazard ratio [HR] = 0.51, 95 % CI: 0.38-0.69, P < 0.0001); median PFS was 8.3 months (95 % CI: 6.7-10.8) versus 5.5 months (95 % CI: 4.3-6.2; HR = 0.48; 95 % CI: 0.37-0.62, P < 0.0001), and ORR was 47.9 % versus 22.7 %, respectively. PRO results favored cemiplimab plus chemotherapy over chemotherapy alone. Improved efficacy over chemotherapy alone was observed in both squamous and non-squamous histology. Safety was consistent with previous reports. CONCLUSION: In this subgroup analysis from EMPOWER-Lung 3 part 2, cemiplimab plus chemotherapy demonstrated clinical benefit over chemotherapy alone in patients with advanced squamous or non-squamous NSCLC with PD-L1 ≥ 1 %.

Guidelines for the diagnosis and treatment of cutaneous squamous cell carcinoma: a GRADE approach for evidence evaluation and recommendations by the Italian Association of Medical Oncology.

Cutaneous squamous cell carcinoma (CSCC) accounts for ∼20%-25% of all skin tumors. Its precise incidence is often challenging to determine due to limited statistics and its incorporation with mucosal forms. While most cases have a favorable prognosis, challenges arise in patients presenting with locally advanced or metastatic forms, mainly appearing in immunocompromised patients, solid organ transplantation recipients, or those facing social difficulties. Traditionally, chemotherapy and targeted therapy were the mainstays for advanced cases, but recent approvals of immunotherapeutic agents like cemiplimab and pembrolizumab have revolutionized treatment options. These guidelines, developed by the Italian Association of Medical Oncologists (AIOM) using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach, aim to guide clinicians in diagnosing, treating, and monitoring patients with CSCC, covering key aspects from primitive tumors to advanced stages, selected by a panel of experts selected by AIOM and other national scientific societies. The incorporation of these guidelines into clinical practice is expected to enhance patient care and address the evolving landscape of CSCC management.

Health-related quality of life in patients with metastatic basal cell carcinoma treated with cemiplimab: Analysis of a phase 2 trial.

BACKGROUND: A phase 2 cemiplimab study (NCT03132636) demonstrated a 24.1% objective response rate in patients diagnosed with metastatic basal cell carcinoma (mBCC) who were not candidates for continued hedgehog inhibitor (HHI) therapy due to intolerance to previous HHI therapy, disease progression while receiving HHI therapy, or having not better than stable disease on HHI therapy after 9 months. Here, health-related quality of life (QoL) for this patient population is reported. METHODS: Adult patients with mBCC were treated with intravenous cemiplimab at a dose of 350 mg every 3 weeks for 5 treatment cycles of 9 weeks/cycle then 4 treatment cycles of 12 weeks/cycle. Patients completed the European Organisation for Research and Treatment of Cancer Quality of Life-Core 30 (QLQ-C30) and Skindex-16 questionnaires at baseline and Day 1 of each cycle. Across Cycles 2 to 9, the overall change from baseline was analyzed using a mixed model with repeated measures. Responder analyses determined clinically meaningful improvement or deterioration (changes ≥10 points) or maintenance across all scales. RESULTS: Patients reported low symptom burden and moderate-to-high functioning at baseline. Maintenance for QLQ-C30 global health status (GHS)/QoL and across all functioning and symptom scales was indicated by overall mean changes from baseline. Clinically meaningful improvement or maintenance was reported at Cycle 2 for GHS/QoL (77%), functioning scales (77% to 86%), and symptom scales (70% to 93%), with similar proportions of improvement or maintenance at Cycles 6 and 9, excluding fatigue. On the Skindex-16, clinically meaningful improvement or maintenance was reported across the emotional, symptom, and functional subscales, in 76%-88% of patients at Cycle 2, which were generally maintained at Cycles 6 and 9. Overall mean changes from baseline showed maintenance across these subscales. CONCLUSIONS: The majority of patients treated with cemiplimab reported improvement or maintenance in GHS/QoL and functioning while maintaining a low symptom burden.