التفاصيل البيبلوغرافية
| العنوان: |
Pembrolizumab versus investigator-choice chemotherapy for ipilimumab-refractory melanoma (KEYNOTE-002): a randomised, controlled, phase 2 trial |
| المؤلفون: |
Ribas, Antoni, Puzanov, Igor, Dummer, Reinhard, Schadendorf, Dirk, Hamid, Omid, Robert, Caroline, Hodi, F Stephen, Schachter, Jacob, Pavlick, Anna C, Lewis, Karl D, Cranmer, Lee D, Blank, Christian U, O'Day, Steven J, Ascierto, Paolo A, Salama, April KS, Margolin, Kim A, Loquai, Carmen, Eigentler, Thomas K, Gangadhar, Tara C, Carlino, Matteo S, Agarwala, Sanjiv S, Moschos, Stergios J, Sosman, Jeffrey A, Goldinger, Simone M, Shapira-Frommer, Ronnie, Gonzalez, Rene, Kirkwood, John M, Wolchok, Jedd D, Eggermont, Alexander, Li, Xiaoyun Nicole, Zhou, Wei, Zernhelt, Adriane M, Lis, Joy, Ebbinghaus, Scot, Kang, S Peter, Daud, Adil |
| المصدر: |
The Lancet Oncology, vol 16, iss 8 |
| بيانات النشر: |
eScholarship, University of California |
| سنة النشر: |
2015 |
| المجموعة: |
University of California: eScholarship |
| مصطلحات موضوعية: |
Clinical Trials and Supportive Activities, Cancer, Clinical Research, 6.1 Pharmaceuticals, Evaluation of treatments and therapeutic interventions, Adolescent, Adult, Aged, 80 and over, Antibodies, Monoclonal, Humanized, Antineoplastic Agents, Antineoplastic Combined Chemotherapy Protocols, Disease Progression, Disease-Free Survival, Drug Resistance, Neoplasm, Female, Humans, Intention to Treat Analysis, Ipilimumab, Kaplan-Meier Estimate, Male, Melanoma, Middle Aged, Skin Neoplasms, Time Factors, Treatment Outcome, Young Adult |
| جغرافية الموضوع: |
908 - 918 |
| الوصف: |
BackgroundPatients with melanoma that progresses on ipilimumab and, if BRAF(V600) mutant-positive, a BRAF or MEK inhibitor or both, have few treatment options. We assessed the efficacy and safety of two pembrolizumab doses versus investigator-choice chemotherapy in patients with ipilimumab-refractory melanoma.MethodsWe carried out a randomised phase 2 trial of patients aged 18 years or older from 73 hospitals, clinics, and academic medical centres in 12 countries who had confirmed progressive disease within 24 weeks after two or more ipilimumab doses and, if BRAF(V600) mutant-positive, previous treatment with a BRAF or MEK inhibitor or both. Patients had to have resolution of all ipilimumab-related adverse events to grade 0-1 and prednisone 10 mg/day or less for at least 2 weeks, an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, and at least one measurable lesion to be eligible. Using a centralised interactive voice response system, we randomly assigned (1:1:1) patients in a block size of six to receive intravenous pembrolizumab 2 mg/kg or 10 mg/kg every 3 weeks or investigator-choice chemotherapy (paclitaxel plus carboplatin, paclitaxel, carboplatin, dacarbazine, or oral temozolomide). Randomisation was stratified by ECOG performance status, lactate dehydrogenase concentration, and BRAF(V600) mutation status. Individual treatment assignment between pembrolizumab and chemotherapy was open label, but investigators and patients were masked to assignment of the dose of pembrolizumab. We present the primary endpoint at the prespecified second interim analysis of progression-free survival in the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT01704287. The study is closed to enrolment but continues to follow up and treat patients.FindingsBetween Nov 30, 2012, and Nov 13, 2013, we enrolled 540 patients: 180 patients were randomly assigned to receive pembrolizumab 2 mg/kg, 181 to receive pembrolizumab 10 mg/kg, and 179 to receive chemotherapy. Based on ... |
| نوع الوثيقة: |
article in journal/newspaper |
| وصف الملف: |
application/pdf |
| اللغة: |
unknown |
| العلاقة: |
qt8j23r3pn; https://escholarship.org/uc/item/8j23r3pnTest |
| الإتاحة: |
https://escholarship.org/uc/item/8j23r3pnTest |
| حقوق: |
public |
| رقم الانضمام: |
edsbas.96055F07 |
| قاعدة البيانات: |
BASE |
