Qualitative Patient Interviews to Characterize the Human Burden of Advanced Basal Cell Carcinoma Following Hedgehog Pathway Inhibitor Treatment.

INTRODUCTION: Evidence of patients' experiences of living with advanced basal cell carcinoma (aBCC) are limited, particularly after hedgehog pathway inhibitor (HHI) treatment. We explored the burden of aBCC on symptoms and patients' everyday lives post HHI treatment. METHODS: In-depth, semi-structured, approximately 1-h qualitative interviews of US patients with aBCC and prior HHI treatment were conducted. Data were assessed using thematic analysis with NVivo 1.0 software. Saturation analysis was performed to ensure all concepts were captured. RESULTS: Fifteen patients (median age, 63 years; locally advanced BCC, n = 9; metastatic BCC, n = 6) were interviewed. A patient-led conceptual model was developed from the responses using 10 symptoms and 15 impact categories (comprising emotional/psychological, physical, and social domains) identified as most commonly discussed and important to patients. Overall, reported impacts were discussed more commonly than reported symptoms. Impacts most commonly discussed were related to emotions (e.g., anxiety, worry, fear [n = 14; 93%]; low mood, depression [n = 12; 80%]) and physical function (e.g., hobbies or leisure activities [n = 13; 87%]). Symptoms most commonly discussed were fatigue and tiredness (n = 14; 93%) and itch (n = 13; 87%). Out of all reported impacts and symptoms, fatigue and tiredness (n = 7, 47%) and anxiety, worry, and fear (n = 6; 40%) were most bothersome to patients. As a descriptive exercise, participant responses were mapped to commonly used patient-reported outcome scales in aBCC clinical trials. Most expressed concepts were captured across two common measures in oncology/skin conditions (European Organization for Research and Treatment of Cancer Quality of Life-Core 30 [EORTC QLQ-C30] and Skindex-16 questionnaires), but sun avoidance and others' perception of skin cancer were not explicitly mentioned by these instruments. CONCLUSION: Patients with aBCC experienced a significant disease burden post first-line HHI therapy, including major emotional and lifestyle impacts. Accordingly, through this study, patients with aBCC highlighted a significant unmet need for second-line treatment options post HHI therapy.

Real-world analysis of cost, treatment patterns, and outcomes of patients with metastatic cutaneous squamous cell carcinoma in the US.

OBJECTIVES: To describe real-world characteristics and treatment patterns of patients with metastatic cutaneous squamous cell carcinoma (mCSCC). METHODS: This retrospective observational study used MarketScan Commercial and Medicare Supplemental claims databases (1/1/2013-7/31/2019). Adult patients with mCSCC who initiated non-immunotherapy systemic treatment (i.e. index event) between 1 January 2014 and 31 December 2018 were assessed for treatment patterns, all-cause and CSCC-related healthcare resource utilization, costs, and mortality . RESULTS: Overall, 207 patients were included in the study(mean age 64.8 years, 76.3% male), 59.4% had prior radiotherapy, and 58.9% had prior CSCC-related surgery. During follow-up, 75.8%, 51.7%, and 35.7% of patients received chemotherapy, radiotherapy, and targeted therapy as first-line treatment, respectively. Cisplatin (32.9%) and carboplatin (22.7%) were the most common chemotherapy agents, and cetuximab (32.4%) was the most common targeted therapy during the first-line.Probability of death (95% CI) at month 6, year 1, and year 2 was 24% (16-32%), 50% (40 - 59%), and 67% (56 - 75%), respectively. Average CSCC-related healthcare costs were $5,354 per person per month (PPPM), with outpatient costs being the major cost driver at 96.4% ($5,160 PPPM). CONCLUSION: During 2014-2018, patients with mCSCC were commonly treated with cisplatin and cetuximab; prognosis was generally poor. These results indicate opportunity for new treatments to improve survival outcomes.

Quality of life with cemiplimab plus chemotherapy for first-line treatment of advanced non-small cell lung cancer: Patient-reported outcomes from phase 3 EMPOWER-Lung 3.

BACKGROUND: EMPOWER-Lung 3, a randomized 2:1 phase 3 trial, showed clinically meaningful and statistically significant overall survival improvement with cemiplimab plus platinum-doublet chemotherapy versus placebo plus chemotherapy for first-line treatment of advanced non-small cell lung cancer. This study evaluated patient-reported outcomes (PROs). METHODS: PROs were assessed at day 1 (baseline), the start of each treatment cycle (every 3 weeks) for the first six doses, and then at start of every three cycles, using the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life-Core 30 (QLQ-C30) and Quality of Life-Lung Cancer Module (QLQ-LC13) questionnaires. Prespecified analyses included a longitudinal mixed-effect model comparing treatment arms and a time to definitive clinically meaningful deterioration (TTD) analysis performed for global health status/quality of life (GHS/QoL) and all scales from the questionnaires. Between-arm TTD comparisons were made using a stratified log-rank test and proportional hazards model. RESULTS: A total of 312 patients were assigned to receive cemiplimab plus platinum-doublet chemotherapy and 154 to receive placebo plus chemotherapy; 391 (83.9%) were male and the median age was 63.0 years (range, 25-84). For pain symptoms (EORTC QLQ-C30), a statistically significant overall improvement from baseline (-4.98, 95% confidence interval [CI] -8.36 to -1.60, p = .004) and a statistically significant delay in TTD (hazard ratio, 0.39; 95% CI, 0.26-0.60, p < .0001) favoring cemiplimab plus chemotherapy were observed. Statistically significant delays in TTD, all favoring cemiplimab plus chemotherapy, were also observed in functioning and symptom scales. A significant overall improvement from baseline in GHS/QoL was seen for cemiplimab plus chemotherapy compared with nonsignificant overall change from baseline for placebo plus chemotherapy (1.69, 95% CI, 0.20-3.19 vs. 1.08, 95% CI, -1.34 to 3.51; between arms, p = .673). No analyses yielded statistically significant PRO results favoring placebo plus chemotherapy for any QLQ-C30 or QLQ-LC13 scale. CONCLUSION: Cemiplimab plus chemotherapy resulted in significant overall improvement in pain symptoms and delayed TTD in cancer-related and lung cancer-specific symptoms and functions.

Patient-reported outcomes with cemiplimab monotherapy for first-line treatment of advanced non-small cell lung cancer with PD-L1 of ≥50%: The EMPOWER-Lung 1 study.

BACKGROUND: In the EMPOWER-Lung 1 trial (ClinicalTrials.gov, NCT03088540), cemiplimab conferred longer survival than platinum-doublet chemotherapy for advanced non-small cell lung cancer (NSCLC) with programmed cell death-ligand 1 (PD-L1) ≥50%. Patient-reported outcomes were evaluated among trial participants. METHODS: Adults with NSCLC and Eastern Cooperative Oncology Group performance status 0 to 1 were randomly assigned cemiplimab 350 mg every 3 weeks or platinum-doublet chemotherapy. At baseline and day 1 of each treatment cycle, patients were administered the European Organization for Research and Treatment of Cancer Quality of Life-Core 30 (QLQ-C30) and Lung Cancer Module (QLQ-LC13) questionnaires. Mixed-model repeated measures analysis estimated overall change from baseline for PD-L1 ≥50% and intention-to-treat populations. Kaplan-Meier analysis estimated time to definitive deterioration. RESULTS: In PD-L1 ≥50% patients (cemiplimab, n = 283; chemotherapy, n = 280), baseline QLQ-C30 and QLQ-LC13 scores showed moderate-to-high functioning and low symptom burden. Change from baseline favored cemiplimab on global health status/quality of life (GHS/QOL), functioning, and most symptom scales. Risk of definitive deterioration across functioning scales was reduced versus chemotherapy; hazard ratios were 0.48 (95% CI, 0.32-0.71) to 0.63 (95% CI, 0.41-0.96). Cemiplimab showed lower risk of definitive deterioration for disease-related (dyspnea, cough, pain in chest, pain in other body parts, fatigue) and treatment-related symptoms (peripheral neuropathy, alopecia, nausea/vomiting, appetite loss, constipation, diarrhea) (nominal p < .05). Results were similar in the intention-to-treat population. CONCLUSIONS: Results support cemiplimab for first-line therapy of advanced NSCLC from the patient's perspective. Improved survival is accompanied by improvements versus platinum-doublet chemotherapy in GHS/QOL and functioning and reduction in symptom burden.

Network meta-analysis of immune-oncology monotherapy as first-line treatment for advanced non-small-cell lung cancer in patients with PD-L1 expression ⩾50.

Background: For patients with advanced non-small-cell lung cancer (NSCLC) and high (⩾50%) programmed cell death-ligand 1 (PD-L1) expression, effective first-line immune-oncology monotherapies with significant survival benefits are approved, cemiplimab being the most recent. In a phase III trial, cemiplimab demonstrated significantly improved overall survival (OS) and progression-free survival (PFS) versus chemotherapy in patients with advanced NSCLC and PD-L1 ⩾50%. A systematic literature review and network meta-analysis (NMA) was conducted to identify/compare the efficacy/safety of cemiplimab versus pembrolizumab or other immune-oncology monotherapies from randomized-controlled trials (RCTs) published in November 2010-2020. Methods: Relevant RCTs were identified by searching databases and conference proceedings as per ISPOR, NICE, and Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. NMA with time-varying hazard ratios (HRs) was performed for OS and PFS. Analyses were conducted for objective response rate (ORR) and safety/tolerability. Fixed-effect models were used due to limited evidence. Various sensitivity analyses were conducted to validate the base case analyses. Results: The feasibility assessment determined that EMPOWER-Lung 1, KEYNOTE-024, and KEYNOTE-042 trials were eligible. IMpower110 was excluded because an incompatible PD-L1 assay (SP142) was used for patient selection. For first-line advanced NSCLC with PD-L1 ⩾50%, cemiplimab was associated with statistically significant improvements in PFS [HR (95% credible interval [CrI]): 0.65 (0.50-0.86), 1-12 months] and ORR [odds ratio (OR) (95% CrI): 1.64 (1.04-2.62)], and comparable OS [HR (95% CrI): 0.77 (0.54-1.10), 1-12 months] versus pembrolizumab. There was no evidence of differences between cemiplimab and pembrolizumab for Grade 3-5 adverse events (AEs) [OR (95% CrI): 1.47 (0.83-2.60)], immune-mediated AEs [1.75 (0.33-7.49)], and all-cause discontinuation due to AEs [1.21 (0.58-2.61)]. Conclusions: Considering the limitations of indirect treatment comparisons, in patients with advanced NSCLC and PD-L1 ⩾50%, cemiplimab monotherapy demonstrated significant improvements in PFS and ORR, comparable OS, and no evidence of differences in safety/tolerability versus pembrolizumab.

Cost-Effectiveness of Cemiplimab Versus Standard of Care in the United States for First-Line Treatment of Advanced Non-small Cell Lung Cancer With Programmed Death-Ligand 1 Expression ≥50.

OBJECTIVES: This study aimed to evaluate the cost-effectiveness, from a US commercial payer perspective, of cemiplimab versus other first-line treatments for advanced non-small cell lung cancer with programmed death-ligand 1 expression ≥50%. METHODS: A 30-year "partitioned survival" model was constructed. Overall survival and progression-free survival were estimated by applying time-varying hazard ratios from a network meta-analysis of randomized clinical trials. Overall survival and progression-free survival were estimated from EMPOWER-Lung 1 (cemiplimab monotherapy vs chemotherapy) and KEYNOTE-024 and KEYNOTE-042 (pembrolizumab monotherapy vs chemotherapy). Drug acquisition costs were based on published 2020 US list prices. A 3% discount rate was applied to life-years, quality-adjusted life-years (QALYs), and costs. A deterministic analysis was performed on the base case; 1-way sensitivity and probabilistic sensitivity analyses assessed model and parameter uncertainties. RESULTS: Cemiplimab was associated with increased time in the "preprogression" (13.08 vs 7.90 and 6.08 months) and "postprogression" (47.30 vs 29.49 and 14.78 months) health states versus pembrolizumab and chemotherapy, respectively. Compared with pembrolizumab and chemotherapy, cemiplimab generated 1.00 (95% CI -0.266 to 2.440) and 1.78 (95% CI 0.607-3.20) incremental QALYs, respectively, with incremental cost-effectiveness ratios of $68 254 and $89 219 per QALY for cemiplimab versus pembrolizumab and cemiplimab versus chemotherapy, respectively. The probability of cemiplimab being cost-effective at a willingness-to-pay threshold of $100 000 to $150 000 per QALY was 62% to 76% versus pembrolizumab and 56% to 84% versus chemotherapy. CONCLUSIONS: Findings suggest that cemiplimab, versus pembrolizumab or versus chemotherapy, is a cost-effective first-line treatment option for advanced non-small cell lung cancer with programmed death-ligand 1 expression ≥50%.

Impact of the treatment crossover design on comparative efficacy in EMPOWER-Lung 1: Cemiplimab monotherapy as first-line treatment of advanced non-small cell lung cancer.

Objectives: In randomized-controlled crossover design trials, overall survival (OS) treatment effect estimates are often confounded by the control group benefiting from treatment received post-progression. We estimated the adjusted OS treatment effect in EMPOWER-Lung 1 (NCT03088540) by accounting for the potential impact of crossover to cemiplimab among controls and continued cemiplimab treatment post-progression. Methods: Patients were randomly assigned 1:1 to cemiplimab 350 mg every 3 weeks (Q3W) or platinum-doublet chemotherapy. Patients with disease progression while on or after chemotherapy could receive cemiplimab 350 mg Q3W for ≤108 weeks. Those who experienced progression on cemiplimab could continue cemiplimab at 350 mg Q3W for ≤108 additional weeks with four chemotherapy cycles added. Three adjustment methods accounted for crossover and/or continued treatment: simplified two-stage correction (with or without recensoring), inverse probability of censoring weighting (IPCW), and rank-preserving structural failure time model (RPSFT; with or without recensoring). Results: In the programmed cell death-ligand 1 ≥50% population (N=563; median 10.8-month follow-up), 38.2% (n=107/280) crossed over from chemotherapy to cemiplimab (71.3%, n=107/150, among those with confirmed progression) and 16.3% (n=46/283) received cemiplimab treatment after progression with the addition of histology-specific chemotherapy (38.7%, n=46/119, among those with confirmed progression). The unadjusted OS hazard ratio (HR) with cemiplimab versus chemotherapy was 0.566 (95% confidence interval [CI]: 0.418, 0.767). Simplified two-stage correction-the most suitable method based on published guidelines and trial characteristics-produced an OS HR of 0.490 (95% CI: 0.365, 0.654) without recensoring and 0.493 (95% CI: 0.361, 0.674) with recensoring. The IPCW and RPSFT methods produced estimates generally consistent with simplified two-stage correction. Conclusions: After adjusting for treatment crossover and continued cemiplimab treatment after progression with the addition of histology-specific chemotherapy observed in EMPOWER-Lung 1, cemiplimab continued to demonstrate a clinically important and statistically significant OS benefit versus chemotherapy, consistent with the primary analysis.

Cost-effectiveness analysis of cemiplimab vs pembrolizumab for treatment of advanced cutaneous squamous cell carcinoma.

BACKGROUND: Most cutaneous squamous cell carcinomas (CSCCs) can be treated with surgical excision or radiation; however, approximately 1% of patients develop advanced disease. In 2018, the FDA approved cemiplimab-rwlc as the first programmed cell death-1 (PD-1) monoclonal antibody for the treatment of patients with metastatic CSCC or locally advanced CSCC who are not candidates for curative surgery or curative radiation. In June 2020, pembrolizumab, another PD-1 monoclonal antibody, was approved for the treatment of patients with recurrent or metastatic CSCC who are not candidates for curative surgery or radiation. We previously reported on the cost-effectiveness of cemiplimab vs historical standard of care for the treatment of advanced CSCC from a US perspective. OBJECTIVE: To estimate the cost-effectiveness of cemiplimab vs pembrolizumab for patients with advanced CSCC in the United States. METHODS: A "partitioned survival" framework was used to assess the cost-effectiveness of cemiplimab vs pembrolizumab. Clinical inputs were based on the most recent data cut of the phase 2 trials for cemiplimab (EMPOWER-CSCC-1; NCT02760498) and pembrolizumab (KEYNOTE-629). Progression-free survival and overall survival were extrapolated using parametric models until all patients had progressed or died. Health state utilities were derived from data collected in the EMPOWER-CSCC-1 trial. Costs included drug acquisition, drug administration, disease management, terminal care, and adverse events and were based on published 2020 US list prices. To assess model uncertainty, 1-way sensitivity and probabilistic sensitivity analyses (PSA) were conducted, alongside scenario analyses evaluating key modeling assumptions. RESULTS: In the base case, cemiplimab resulted in an incremental gain of 3.44 life-years (discounted) and incremental cost-effectiveness ratio (ICER) of $130,329 per quality-adjusted life-year (QALY) vs pembrolizumab. At a willingness-to-pay threshold of $150,000/QALY, PSA indicated a 71% probability that cemiplimab is cost-effective when compared with pembrolizumab. Scenario analysis resulted in ICERs ranging from $115,909 to $187,374. CONCLUSIONS: Findings suggest that cemiplimab is a cost-effective treatment for patients with advanced CSCC, compared with pembrolizumab. These results should be interpreted cautiously in the absence of head-to-head trials; however, in the absence of such data, these results can be used to inform health care decisions over resource allocation. DISCLOSURES: This study was supported by Regeneron Pharmaceuticals, Inc., and Sanofi. Paul, Cope, Keeping, Mojebi, and Ayers are employees of PRECISIONheor, which received funding to produce this work. Chen, Kuznik, and Xu are employees and stockholders of Regeneron Pharmaceuticals, Inc. Sasane is an employee and stockholder of Sanofi, Inc. Konidaris, Atsou, and Guyot are employees of Sanofi, Inc. The authors were responsible for all content and editorial decisions and received no honoraria related to the development of this publication.

Assessing the Value of Cemiplimab for Adults With Advanced Cutaneous Squamous Cell Carcinoma: A Cost-Effectiveness Analysis.

OBJECTIVES: To evaluate the cost-effectiveness of cemiplimab in patients with advanced cutaneous squamous cell carcinoma (CSCC) from a payer perspective in the United States. METHODS: A partitioned survival model was developed to assess the cost-effectiveness of cemiplimab versus historical standard of care (SOC). All inputs were identified based on a systematic literature review, supplemented by expert opinion where necessary. Clinical inputs for cemiplimab were based on individual patient data from a cemiplimab phase 2 single-arm trial (NCT27060498). For SOC, analysis was based on a pooled analysis of single-arm clinical trials and retrospective studies evaluating chemotherapy and epidermal growth factor receptor inhibitors (cetuximab, erlotinib, and gefitinib) identified via a systematic literature review (6 of the 27 included studies). Overall survival and progression-free survival were extrapolated over a lifetime horizon. Costs were included for drug acquisition, drug administration, management of adverse events, subsequent therapy, disease management, and terminal care. Unit costs were based on published 2019 US list prices. RESULTS: In the base case, cemiplimab versus SOC resulted in an incremental cost-effectiveness ratio of $99 447 per quality adjusted-life year (QALY), where incremental costs and QALYs were $372 108 and 3.74, respectively. At a willingness-to-pay threshold of $150 000/QALY, the probabilistic sensitivity analysis suggests a 90% probability that cemiplimab is cost-effective compared to SOC. Scenario analyses resulted in incremental cost-effectiveness ratios ranging from $90 590 to $148 738. CONCLUSIONS: Compared with historical SOC, cemiplimab is a cost-effective use of US payer resources for the treatment of advanced CSCC and is expected to provide value for money.

Comparative efficacy of cemiplimab versus other systemic treatments for advanced cutaneous squamous cell carcinoma.

Aim: To estimate the comparative efficacy of cemiplimab, a programmed cell death protein 1 inhibitor, versus EGFR inhibitors, pembrolizumab and platinum-based chemotherapy in terms of overall survival (OS) and progression-free survival. Patients & methods: We performed an indirect treatment comparison of cemiplimab and other available systemic therapies for patients with advanced cutaneous squamous cell carcinoma. Results: Cemiplimab was associated with benefits in OS (hazard ratios range: 0.07-0.52) and progression-free survival (hazard ratios range: 0.30-0.67) versus EGFR inhibitors and pembrolizumab (data from KEYNOTE-629). Cemiplimab was more efficacious versus platinum-based chemotherapy in terms of OS. Conclusion: Cemiplimab may offer improvements in survival for advanced cutaneous squamous cell carcinoma patients compared with existing systemic therapies.

A Retrospective Observational Study to Determine Baseline Characteristics and Early Prescribing Patterns for Patients Receiving Alirocumab in UK Clinical Practice.

BACKGROUND: Alirocumab is a fully human monoclonal antibody to proprotein convertase subtilisin/kexin type 9 (PCSK9) and has been previously shown, in the phase III ODYSSEY clinical trial program, to provide significant lowering of low-density lipoprotein cholesterol (LDL-C) and reduction in risk of major adverse cardiovascular events. However, real-world evidence to date is limited. OBJECTIVE: The primary objective was to describe baseline characteristics, clinical history, and prior lipid-lowering therapy (LLT) use of patients initiated on alirocumab in UK clinical practice following publication of health technology appraisal (HTA) body recommendations. Secondary objectives included description of alirocumab use and lipid parameter outcomes over a 4-month follow-up period. METHODS: In this retrospective, single-arm, observational, multicenter study, data were collected for 150 patients initiated on alirocumab. RESULTS: Mean (standard deviation; SD) age of patients was 61.4 (10.5) years and baseline median (interquartile range; IQR) LDL-C level was 4.8 (4.2-5.8) mmol/l. Alirocumab use occurred predominantly in patients with heterozygous familial hypercholesterolemia (HeFH) (n = 100/150, 66%) and those with statin intolerance (n = 123/150, 82%). Most patients started on alirocumab 75 mg (n = 108/150 [72%]) and 35 (23.3%) were up-titrated to 150 mg. Clinically significant reductions in atherogenic lipid parameters were observed with alirocumab, including LDL-C (median [IQR] change from baseline, - 53.6% [- 62.9 to - 34.9], P < 0.001). CONCLUSION: This study highlights the unmet need for additional LLT in patients with uncontrolled hyperlipidemia and demonstrates the clinical utility of alirocumab in early real-world practice, where dosing flexibility is an important attribute of this therapeutic option.

Cost Effectiveness of IDegLira vs. Alternative Basal Insulin Intensification Therapies in Patients with Type 2 Diabetes Mellitus Uncontrolled on Basal Insulin in a UK Setting.

OBJECTIVES: Once-daily insulin degludec/liraglutide (IDegLira) is the first basal insulin and glucagon like peptide-1 receptor agonist combined in one delivery device. Our aim was to investigate the cost effectiveness of IDegLira vs. basal insulin intensification therapies for patients with type 2 diabetes mellitus uncontrolled on basal insulin (glycosylated haemoglobin; HbA1c >7.5 %; 58 mmol/mol) in a UK setting. RESEARCH DESIGN AND METHODS: Baseline cohort and clinical parameters were sourced from a pooled analysis comparing IDegLira with basal insulin plus liraglutide and basal-bolus therapy, and from the DUAL™ V trial comparing IDegLira with up-titrated insulin glargine (IGlar; Lantus(®)). The CORE Diabetes Model simulated lifetime costs and outcomes with IDegLira vs. these comparators from a UK healthcare payers' perspective. All costs were expressed in 2015 GBP. Sensitivity analyses were performed to assess the impact of key parameters in the model. RESULTS: Treatment with IDegLira resulted in mean increases in quality-adjusted life-years (QALYs) of 0.12, 0.41 and 0.24 vs. basal insulin plus liraglutide, basal-bolus therapy and up-titrated IGlar, respectively. IDegLira was associated with lower costs of £971 and £1698 vs. basal insulin plus liraglutide and basal-bolus therapy, respectively, and increased costs of £1441 vs. up-titrated IGlar. IDegLira was dominant, i.e., both more effective and less costly vs. basal insulin plus liraglutide and basal-bolus therapy, and highly cost effective vs. up-titrated IGlar with an incremental cost-effectiveness ratio of £6090/QALY gained. CONCLUSIONS: Once-daily IDegLira may be considered a cost-effective treatment option for prescribers, to improve glycaemic control for type 2 diabetes patients uncontrolled on basal insulin without an increased risk of hypoglycaemia or weight gain, and without adding to their injection burden.