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Gefitinib for patients with incurable cutaneous squamous cell carcinoma: A single-arm phase II clinical trial.

ABSTRACT: Preclinical data demonstrate a key role for the epidermal growth factor receptor (EGFR) in the carcinogenesis of cutaneous squamous cell carcinomas (CSCCs). There are, however, limited data on the efficacy of EGFR inhibitors in incurable, recurrent, and/or metastatic CSCC.To determine the response rate to gefitinib in patients with CSCC not amenable to curative therapy including surgery or radiation.This was a single-arm phase II study. A total of 40 patients were treated with gefitinib, 250 mg orally daily, until disease progression or intolerable toxicities. The prespecified target response rate of interest was 20%.The overall response rate was 16% (95% confidence interval, 0.06-0.32; 6 partial responses in 37 evaluable patients). An additional 13 patients (35%) had stable disease at 8 weeks. The median durations of response and progression-free survival were 31.4 months (95% confidence interval, 3.91-not applicable) and 3.8 months (95% confidence interval, 2.2-5.7), respectively. The side effect profile was consistent with the previous experience with gefitinib in other tumor types.This was a single-institution, single-arm study. The prespecified target response rate was not met.Gefitinib demonstrated modest activity in incurable CSCC, with a favorable adverse event profile.

SUBMITTER: William WN

PROVIDER: S-EPMC5685879 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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Gefitinib for patients with incurable cutaneous squamous cell carcinoma: A single-arm phase II clinical trial.

William William N WN Feng Lei L Ferrarotto Renata R Ginsberg Lawrence L Kies Merrill M Lippman Scott S Glisson Bonnie B Kim Edward S ES

Journal of the American Academy of Dermatology 20170928 6

<h4>Background</h4>Preclinical data demonstrate a key role for the epidermal growth factor receptor (EGFR) in the carcinogenesis of cutaneous squamous cell carcinomas (CSCCs). There are, however, limited data on the efficacy of EGFR inhibitors in incurable, recurrent, and/or metastatic CSCC.<h4>Objective</h4>To determine the response rate to gefitinib in patients with CSCC not amenable to curative therapy including surgery or radiation.<h4>Methods</h4>This was a single-arm phase II study. A tota ...[more]

PMID: 28964539

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Project description:BackgroundCemiplimab has shown substantial antitumour activity in patients with metastatic cutaneous squamous cell carcinoma. Patients with locally advanced cutaneous squamous cell carcinoma have poor prognosis with conventional systemic therapy. We present a primary analysis of the safety and antitumour activity of cemiplimab in patients with locally advanced cutaneous squamous cell carcinoma.MethodsThis pivotal open-label, phase 2, single-arm trial was done across 25 outpatient clinics, primarily at academic medical centres, in Australia, Germany, and the USA. Eligible patients (aged ?18 years with histologically confirmed locally advanced cutaneous squamous cell carcinoma and an Eastern Cooperative Oncology Group performance status of 0-1) received cemiplimab 3 mg/kg intravenously over 30 min every 2 weeks for up to 96 weeks. Tumour measurements were done every 8 weeks. The primary endpoint was objective response, defined as the proportion of patients with complete or partial response, according to independent central review as per Response Evaluation Criteria in Solid Tumors version 1.1 for radiological scans and WHO criteria for medical photography. Data cutoff was Oct 10, 2018, when the fully enrolled cohort reached the prespecified timepoint for the primary analysis. Analyses were done as per the intention-to-treat principle. The safety analysis comprised all patients who received at least one dose of cemiplimab. This study is registered with ClinicalTrials.gov, number NCT02760498.FindingsBetween June 14, 2016, and April 25, 2018, 78 patients were enrolled and treated with cemiplimab. The median duration of study follow-up was 9·3 months (IQR 5·1-15·7) at the time of data cutoff. An objective response was observed in 34 (44%; 95% CI 32-55) of 78 patients. The best overall response was ten (13%) patients with a complete response and 24 (31%) with a partial response. Grade 3-4 treatment-emergent adverse events occurred in 34 (44%) of 78 patients; the most common were hypertension in six (8%) patients and pneumonia in four (5%). Serious treatment-emergent adverse events occurred in 23 (29%) of 78 patients. One treatment-related death was reported that occurred after onset of aspiration pneumonia.InterpretationCemiplimab showed antitumour activity and an acceptable safety profile in patients with locally advanced cutaneous squamous cell carcinoma for whom there was no widely accepted standard of care.FundingRegeneron Pharmaceuticals and Sanofi.

Project description:BackgroundBladder and urinary tract cancers account for approximately 21,000 new diagnoses and 5,000 deaths annually in the UK. Approximately 90% are transitional cell carcinomas where advanced disease is treated with platinum based chemotherapy and PD-1/PD-L1 directed immunotherapy. Urinary tract squamous cell carcinoma (UTSCC) accounts for about 5% of urinary tract cancers overall making this a rare disease. We have yet to establish definitive systemic treatment options for advanced UTSCC. Preliminary translational data, from UTSCC patient tumour samples, indicate high PD-L1 expression and tumour infiltrating lymphocytes in a proportion of cases. Both of these features are associated with differential gene expression consistent with a tumour/immune microenvironment predicted to be susceptible to immune checkpoint directed immunotherapy which we will evaluate in the AURORA trial.MethodsAURORA is a single arm, open-label, multicentre,UK phase II clinical trial. 33 patients will be recruited from UK secondary care sites. Patients with UTSCC, suitable for treatment with palliative intent, will receive atezolizumab PD-L1 directed immunotherapy (IV infusion, 1680 mg, every 28 days) for one year if tolerated. Response assessment, by cross sectional imaging will occur every 12 weeks. AURORA uses a Simon's 2-stage optimal design with best overall objective response rate (ORR, by RECIST v1.1) at a minimum of 12 weeks from commencing treatment as the primary endpoint. Secondary endpoints will include overall survival, progression-free survival, duration of response, magnitude of response using waterfall plots of target lesion measurements, quality of life using the EORTC QLQ-C30 tool, safety and tolerability (CTCAE v5) and evaluation of potential biomarkers of treatment response including PD-L1 expression. Archival tumour samples and blood samples will be collected for translational analyses.DiscussionIf this trial shows atezolizumab to be safe and effective it may lead to a future late phase randomised controlled trial in UTSCC. Ultimately, we hope to provide a new option for treatment for such patients.Trial registrationsEudraCT Number: 2021-001995-32 (issued 8th September 2021); ISRCTN83474167 (registered 11 May 2022); NCT05038657 (issued 9th September 2021).

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Gefitinib for patients with incurable cutaneous squamous cell carcinoma: A single-arm phase II clinical trial.

Publications

Gefitinib for patients with incurable cutaneous squamous cell carcinoma: A single-arm phase II clinical trial.

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