دورية أكاديمية
Final analysis of phase II results with cemiplimab in metastatic basal cell carcinoma after hedgehog pathway inhibitors.
| العنوان: | Final analysis of phase II results with cemiplimab in metastatic basal cell carcinoma after hedgehog pathway inhibitors. |
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| المؤلفون: | Lewis KD; Department of Medicine-Medical Oncology, University of Colorado School of Medicine, Aurora, USA. Electronic address: karl.lewis@regeneron.com., Peris K; Department of Medicine and Translational Surgery, Dermatology, Università Cattolica del Sacro Cuore, Rome; Department of Medical and Surgical Sciences, Dermatology, Fondazione Policlinico Universitario A. Gemelli-IRCCS, Rome, Italy., Sekulic A; Department of Dermatology, Mayo Clinic, Scottsdale, USA., Stratigos AJ; First Department of Dermatology-Venereology, National and Kapodistrian University of Athens, Andreas Sygros Hospital, Athens, Greece., Dunn L; Department of Medicine, Head and Neck Medical Oncology, Memorial Sloan Kettering Cancer Center, New York., Eroglu Z; Department of Cutaneous Oncology, Moffitt Cancer Center, Tampa., Chang ALS; Dermatology Department, Stanford University School of Medicine, Redwood City., Migden MR; Department of Dermatology and Head and Neck Surgery, University of Texas MD Anderson Cancer Center, Houston; Department of Head and Neck Surgery, University of Texas MD Anderson Cancer Center, Houston., Yoo SY; Regeneron Pharmaceuticals, Inc., Tarrytown, USA., Mohan K; Regeneron Pharmaceuticals, Inc., Tarrytown, USA., Coates E; Regeneron Pharmaceuticals, Inc., Tarrytown, USA., Okoye E; Regeneron Pharmaceuticals, Inc., Tarrytown, USA., Bowler T; Regeneron Pharmaceuticals, Inc., Tarrytown, USA., Baurain JF; Department of Medical Oncology, Cliniques Universitaires Saint-Luc and Université Catholique de Louvain, Brussels., Bechter O; Department of General Medical Oncology, University Hospitals, Leuven, Belgium., Hauschild A; Department of Dermatology, University Hospital Schleswig-Holstein (UKSH), Kiel, Germany., Butler MO; Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario, Canada., Hernandez-Aya L; Division of Medical Oncology, Department of Medicine, Washington University School of Medicine, St Louis, USA., Licitra L; Department of Medical Oncology Head and Neck Cancer, Istituto Nazionale dei Tumori, Milan; Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy., Neves RI; Division of Plastic Surgery, Penn State Milton S. Hershey Medical Center, Hershey., Ruiz ES; Department of Dermatology, Brigham and Women's Hospital, Harvard Medical School, Boston, USA., Seebach F; Regeneron Pharmaceuticals, Inc., Tarrytown, USA., Lowy I; Regeneron Pharmaceuticals, Inc., Tarrytown, USA., Goncalves P; Regeneron Pharmaceuticals, Inc., Tarrytown, USA., Fury MG; Regeneron Pharmaceuticals, Inc., Tarrytown, USA. |
| المصدر: | Annals of oncology : official journal of the European Society for Medical Oncology [Ann Oncol] 2024 Feb; Vol. 35 (2), pp. 221-228. Date of Electronic Publication: 2023 Dec 09. |
| نوع المنشور: | Clinical Trial, Phase II; Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Country of Publication: England NLM ID: 9007735 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1569-8041 (Electronic) Linking ISSN: 09237534 NLM ISO Abbreviation: Ann Oncol Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2020- : London : Elsevier Original Publication: Dordrecht ; Boston : Kluwer Academic Publishers, c1990- |
| مواضيع طبية MeSH: | Antineoplastic Agents*/therapeutic use , Carcinoma, Basal Cell*/drug therapy , Carcinoma, Basal Cell*/chemically induced , Skin Neoplasms*/drug therapy , Skin Neoplasms*/pathology , Antibodies, Monoclonal, Humanized*, Adult ; Humans ; Male ; Middle Aged ; Aged ; Female ; Hedgehog Proteins ; Ligands ; Disease Progression ; Amides/therapeutic use |
| مستخلص: | Background: Metastatic basal cell carcinoma (mBCC) is a rare condition with no effective second-line treatment options. Cemiplimab is an immune checkpoint inhibitor that blocks the binding of programmed cell death-1 (PD-1) to its ligands, programmed death-ligand 1 (PD-L1) and programmed death-ligand 2 (PD-L2). Here, we present the final analysis of cemiplimab in patients with mBCC after first-line hedgehog pathway inhibitor (HHI) treatment (NCT03132636). Patients and Methods: In this open-label, single-arm, phase II study, adults with mBCC and Eastern Cooperative Oncology Group performance status ≤1, post-HHI treatment, received cemiplimab 350 mg intravenously every 3 weeks for ≤93 weeks or until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR) by independent central review (ICR). Duration of response (DOR) was a key secondary endpoint. Other secondary endpoints were ORR per investigator assessment, progression-free survival (PFS), overall survival (OS), complete response rate, safety, and tolerability. Results: Fifty-four patients were enrolled: 70% were male and the median age of patients was 64 [interquartile range (IQR) 57.0-73.0] years. The median duration of follow-up was 8 months (IQR 4-21 months). The ORR per ICR was 22% [95% confidence interval (CI) 12% to 36%], with 2 complete responses and 10 partial responses. Among responders, the median time to response per ICR was 3 months (IQR 2-7 months). The estimated median DOR per ICR was not reached [95% CI 10 months-not evaluable (NE)]. The disease control rate was 63% (95% CI 49% to 76%) per ICR and 70% (95% CI 56% to 82%) per investigator assessment. The median PFS per ICR was 10 months (95% CI 4-16 months); the median OS was 50 months (95% CI 28 months-NE). The most common treatment-emergent adverse events were fatigue [23 (43%)] and diarrhoea [20 (37%)]. There were no treatment-related deaths. Conclusions: Cemiplimab demonstrated clinically meaningful antitumour activity, including durable responses, and an acceptable safety profile in patients with mBCC who had disease progression on or intolerance to HHI therapy. (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.) |
| فهرسة مساهمة: | Keywords: PD-1; cemiplimab; hedgehog inhibitor; immunotherapy; metastatic basal cell carcinoma |
| سلسلة جزيئية: | ClinicalTrials.gov NCT03132636 |
| المشرفين على المادة: | 6QVL057INT (cemiplimab) 0 (Hedgehog Proteins) 0 (Ligands) 0 (Antineoplastic Agents) 0 (Amides) 0 (Antibodies, Monoclonal, Humanized) |
| تواريخ الأحداث: | Date Created: 20231210 Date Completed: 20240214 Latest Revision: 20240214 |
| رمز التحديث: | 20240214 |
| DOI: | 10.1016/j.annonc.2023.10.123 |
| PMID: | 38072158 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1569-8041 |
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| DOI: | 10.1016/j.annonc.2023.10.123 |