Three-year survival, correlates and salvage therapies in patients receiving first-line pembrolizumab for advanced Merkel cell carcinoma
| العنوان: | Three-year survival, correlates and salvage therapies in patients receiving first-line pembrolizumab for advanced Merkel cell carcinoma |
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| المؤلفون: | Evan J. Lipson, Ragini R. Kudchadkar, Sunil Reddy, Tomoko Akaike, Thomas Olencki, William H. Sharfman, Philip Friedlander, Steven P. Fling, Mizuho Kalabis, Candice D. Church, Kari Kendra, Michi M. Shinohara, Adil Daud, Adam I. Riker, Harriet M. Kluger, Elad Sharon, Melissa Amber Burgess, Janis M. Taube, Paul Nghiem, Brent A. Hanks, Suzanne L. Topalian, Blanca Homet Moreno, Andrew S. Brohl, Brian C. Boulmay, Martin A. Cheever, Bob Salim, Erin Jensen, Shailender Bhatia, Nirasha Ramchurren |
| المصدر: | Journal for ImmunoTherapy of Cancer, Vol 9, Iss 4 (2021) Journal for immunotherapy of cancer, vol 9, iss 4 Journal for Immunotherapy of Cancer |
| بيانات النشر: | BMJ, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Male, 0301 basic medicine, Oncology, Cancer Research, Skin Neoplasms, Time Factors, medicine.medical_treatment, Programmed Cell Death 1 Receptor, Pembrolizumab, 0302 clinical medicine, Stable Disease, Cancer immunotherapy, Monoclonal, 80 and over, Immunology and Allergy, Humanized, Immune Checkpoint Inhibitors, 6.2 Cellular and gene therapies, RC254-282, Cancer, Aged, 80 and over, Clinical/Translational Cancer Immunotherapy, Merkel cell carcinoma, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Middle Aged, Progression-Free Survival, 6.1 Pharmaceuticals, 030220 oncology & carcinogenesis, Disease Progression, Molecular Medicine, Female, immunotherapy, medicine.medical_specialty, Clinical Trials and Supportive Activities, Immunology, Antibodies, Monoclonal, Humanized, Antibodies, 03 medical and health sciences, Clinical Research, Internal medicine, medicine, Humans, Neoplasm Staging, Aged, Salvage Therapy, Pharmacology, Chemotherapy, business.industry, Carcinoma, Evaluation of treatments and therapeutic interventions, Immunotherapy, medicine.disease, Carcinoma, Merkel Cell, 030104 developmental biology, Tumor progression, Merkel Cell, Skin cancer, business |
| الوصف: | BackgroundMerkel cell carcinoma (MCC) is an aggressive skin cancer associated with poor survival. Programmed cell death-1 (PD-1) pathway inhibitors have shown high rates of durable tumor regression compared with chemotherapy for MCC. The current study was undertaken to assess baseline and on-treatment factors associated with MCC regression and 3-year survival, and to explore the effects of salvage therapies in patients experiencing initial non-response or tumor progression after response or stable disease following first-line pembrolizumab therapy on Cancer Immunotherapy Trials Network-09/KEYNOTE-017.MethodsIn this multicenter phase II trial, 50 patients with advanced unresectable MCC received pembrolizumab 2 mg/kg every 3 weeks for ≤2 years. Patients were followed for a median of 31.8 months.ResultsOverall response rate to pembrolizumab was 58% (complete response 30%+partial response 28%; 95% CI 43.2 to 71.8). Among 29 responders, the median response duration was not reached (NR) at 3 years (range 1.0+ to 51.8+ months). Median progression-free survival (PFS) was 16.8 months (95% CI 4.6 to 43.4) and the 3-year PFS was 39.1%. Median OS was NR; the 3-year OS was 59.4% for all patients and 89.5% for responders. Baseline Eastern Cooperative Oncology Group performance status of 0, greater per cent tumor reduction, completion of 2 years of treatment and low neutrophil-to-lymphocyte ratio were associated with response and longer survival. Among patients with initial disease progression or those who developed progression after response or stable disease, some had extended survival with subsequent treatments including chemotherapies and immunotherapies.ConclusionsThis study represents the longest available follow-up from any first-line anti-programmed death-(ligand) 1 (anti-PD-(L)1) therapy in MCC, confirming durable PFS and OS in a proportion of patients. After initial tumor progression or relapse following response, some patients receiving salvage therapies survived. Improving the management of anti-PD-(L)1-refractory MCC remains a challenge and a high priority.Trial registration numberNCT02267603. |
| وصف الملف: | application/pdf |
| تدمد: | 2051-1426 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::272adca2addf0d58650483b69b745a95Test https://doi.org/10.1136/jitc-2021-002478Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....272adca2addf0d58650483b69b745a95 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20511426 |
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