Integrated analysis of a phase 2 study of cemiplimab in advanced cutaneous squamous cell carcinoma: extended follow-up of outcomes and quality of life analysis

Rischin, Danny; Schmults, Chrysalyne D.; Guminski, Alexander; Chang, Anne Lynn S.; Lewis, Karl D.; Lim, Annette; Hernandez‐Aya, Leonel F.; Hughes, Brett; Schadendorf, Dirk; Hauschild, Axel; Thai, Alesha; Stankevich, Elizabeth; Booth, Jocelyn; Yoo, Suk Young; Li, Siyu; Chen, Zhe; Okoye, Emmanuel Ikechukwu; Chen, Chieh I.; Mastey, Vera; Sasané, Medha; Lowy, Israel; Fury, Matthew G.; Migden, Michael R.

doi:10.1136/jitc-2021-002757

Cited by 68 publications

(87 citation statements)

References 25 publications

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“…Moreover, we observed that two patients who initially presented with SD, subsequently achieved a response (one PR, one CR), suggesting that responses to PD-1 therapy may deepen over time, as seen in other malignancies. 38 39 Despite these promising findings, there remains the question of whether tumor regressions will continue once PD-1 therapy has been stopped. In a retrospective study of 110 BCC patients who achieved CR to HHI but then discontinued treatment, nearly half of the patients (48.1%) experienced a relapse while off treatment.…”

Section: Discussionmentioning

confidence: 99%

Clinical activity of PD-1 inhibition in the treatment of locally advanced or metastatic basal cell carcinoma

Nallagangula

Choi

et al. 2022

J Immunother Cancer

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BackgroundBasal cell carcinoma (BCC) is the most common malignancy worldwide, yet the management of patients with advanced or metastatic disease is challenging, with limited treatment options. Recently, programmed death receptor 1 (PD-1) inhibition has demonstrated activity in BCC after prior Hedgehog inhibitor treatment.MethodsWe conducted a multicenter, retrospective analysis of BCC patients treated with PD-1 inhibitor therapy. We examined the efficacy and safety of PD-1 therapy, as well as clinical and pathological variables in association with outcomes. Progression-free survival (PFS), overall survival (OS) and duration of response (DOR) were calculated using Kaplan-Meier methodology. Toxicity was graded per Common Terminology Criteria for Adverse Events V.5.0.ResultsA total of 29 patients with BCC who were treated with PD-1 inhibition were included for analysis, including 20 (69.0%) with locally advanced and 9 (31.0%) with metastatic disease. The objective response rate was 31.0%, with five partial responses (17.2%), and four complete responses (13.8%). Nine patients had stable disease (31.0%), with a disease control rate of 62.1%. The median DOR was not reached. Median PFS was 12.2 months (95% CI 0.0 to 27.4). Median OS was 32.4 months (95% CI 18.1 to 46.7). Two patients (6.9%) developed grade 3 or higher toxicity, while four patients (13.8%) discontinued PD-1 inhibition because of toxicity. Higher platelets (p=0.022) and any grade toxicity (p=0.024) were significantly associated with disease control rate.ConclusionsThe clinical efficacy of PD-1 inhibition among patients with advanced or metastatic BCC in this real-world cohort were comparable to published trial data. Further investigation of PD-1 inhibition is needed to define its optimal role for patients with this disease.

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Section: Discussionmentioning

confidence: 99%

Clinical activity of PD-1 inhibition in the treatment of locally advanced or metastatic basal cell carcinoma

Nallagangula

Choi

et al. 2022

J Immunother Cancer

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“…33 With a median follow up of 15.7 (range 0.6-36.1) months, the objective response rate was reported as 46.1% (95% CI: 38.9-53.4), the number of complete responses had increased from 7% to 16.1%, the durable disease control rate was 61% (95% CI: 53.3-67.6) and median OS was not reached. 33 High tumour mutational burden is associated with durable response to immunotherapies, from which precedence of excellent survival has been demonstrated in other cancers such as advanced melanoma, with cSCC known to have the highest tumour mutational burden of all cancers. 34,35 In Australia, immunotherapy is not yet available for reimbursement under the Pharmaceutical Benefits Scheme.…”

Section: Discussionmentioning

confidence: 97%

Clinicopathological characteristics and clinical morbidity in high‐risk head and neck cutaneous squamous cell carcinoma patients in Western Australia

Grover

Flukes

Jacques

et al. 2022

Internal Medicine Journal

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Background: There is no registry data on morbidity and mortality of high-risk cutaneous squamous cell carcinoma (cSCC) in Australia.Aim: To examine the clinicopathological features, mortality and morbidity in high-risk cSCC patients in Western Australia (WA).Methods: A retrospective cohort study was conducted through hospital record review on cSCC patients discussed at multidisciplinary meetings at the two largest WA hospitals between March 2015 and December 2016.Results: Of 141 patients, 129 were evaluable, with median follow up of 43.9 (range 3.0-53.2) months. Patients were predominantly older males (84%) with significant comorbidities (Charlson Comorbidity Index (CCI) ≥5; 76%) and history of previous nonmelanoma skin cancer (57%) with advanced disease (57% stage IV without distant metastasis; American Joint Committee on Cancer, 7th edition). Pathological high-risk features were common including nodal extracapsular extension (47%) and cranial nerve involvement (16%). Clinical morbidity was significant with a median of 2 (range 0-13) excisions and 2 (range 0-21) cSCC-related hospitalisations for any cSCC event following the index case discussion. Recurrences of the primary index lesion occurred in 60% of patients and 20% had ≥2 recurrences. Median overall survival for patients with nonmetastatic disease was 39.8 (range 25.9-53.7) months and 16.1 (range 0.2-32.0) months for metastatic disease. CCI ≥5, advanced nodal stage and ≥2 recurrences were significantly associated with mortality on multivariable analyses (P < 0.05). Nodal extracapsular extension and any recurrences were identified as significant risk factors for disease-specific mortality on multivariable analyses (P < 0.05). Conclusion:High-risk cSCC patients have significant health needs represented by high-baseline comorbidities, multiplicity of cSCC events and the number of healthcareassociated interventions. There is an unmet need for robust cancer data collection.

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“…Cemiplimab is a high-affinity human monoclonal antibody that blocks PD-1 directly ( 44 ). Previous primary studies demonstrated that cemiplimab showed substantial antitumor activity, durable response, and an acceptable safety profile in patients with advanced cutaneous squamous cell carcinoma ( 45 , 46 ). In addition, the EMPOWER-Lung 1 trial proved for the first time that cemiplimab appears to be an attractive choice for the treatment of advanced NSCLC as a first-line option.…”

Section: Discussionmentioning

confidence: 99%

Comparative Efficacy and Safety of Anti-PD-1/PD-L1 for the Treatment of Non-Small Cell Lung Cancer: A Network Meta-Analysis of 13 Randomized Controlled Studies

et al. 2022

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ObjectiveThe present network meta-analysis (NMA) was conducted to summarize the direct and indirect evidence of common programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) inhibitors including avelumab, atezolizumab, cemiplimab, nivolumab, and pembrolizumab for the treatment of non-small cell lung cancer (NSCLC) patients and further to determine the optimal therapeutic regimen.MethodsWe performed a systematic literature search to identify all potentially eligible studies in PubMed, Embase, and the Cochrane Library until August 7, 2021. The primary outcome was overall survival (OS), and the second outcome was treatment-related adverse events (TRAEs). We used random-effects model to conduct direct and network meta-analyses, which were performed by using RevMan 5.3 and R version 3.6.1, respectively.ResultsDirect meta-analysis suggested that atezolizumab, cemiplimab, nivolumab, or pembrolizumab significantly improved OS compared with chemotherapy (CT), and NMA further established that atezolizumab [hazard ratio (HR), 0.77; 95% CrI, 0.62–0.96], nivolumab (HR, 0.75; 95% CrI, 0.62–0.93), or pembrolizumab (HR, 0.71; 95% Credible interval (Crl), 0.57–0.89) significantly and cemiplimab (HR, 0.68; 95% CrI, 0.46–1.02) numerically improved OS compared with CT. Meanwhile, NMA also indicated that cemiplimab was numerically superior to other PD-1/PD-L1 agents. Moreover, avelumab, atezolizumab, cemiplimab, nivolumab, and pembrolizumab were found to have fewer TRAEs compared with CT in direct meta-analysis, which were supported by the results from the NMA. Meanwhile, surface under the cumulative ranking curve (SUCRA) and ranking probability suggested that cemiplimab provided the most favorable balance between efficacy and safety, with the first ranking for the OS.ConclusionsBased on available evidence, cemiplimab may have the most favorable risk–benefit ratio for NSCLC patients compared with other common therapeutic management. However, future research with a large-scale, high-quality, and mature follow-up is needed to further determine which agents should be preferentially selected for NSCLC patients due to the limitations of our NMA and variations of eligible studies in treatment line and PD-L1 status.

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Integrated analysis of a phase 2 study of cemiplimab in advanced cutaneous squamous cell carcinoma: extended follow-up of outcomes and quality of life analysis

Cited by 68 publications

References 25 publications

Clinical activity of PD-1 inhibition in the treatment of locally advanced or metastatic basal cell carcinoma

Clinical activity of PD-1 inhibition in the treatment of locally advanced or metastatic basal cell carcinoma

Clinicopathological characteristics and clinical morbidity in high‐risk head and neck cutaneous squamous cell carcinoma patients in Western Australia

Comparative Efficacy and Safety of Anti-PD-1/PD-L1 for the Treatment of Non-Small Cell Lung Cancer: A Network Meta-Analysis of 13 Randomized Controlled Studies

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