Phase II study of ipilimumab and nivolumab in leptomeningeal carcinomatosis
| Autor: | Scott L. Carter, Daniel P. Cahill, Pamela S. Jones, Brian V. Nahed, Albert E. Kim, Christopher Alvarez-Breckenridge, Ugonma Chukwueke, Wendy Y. Chen, Beth Overmoyer, Matthew R. Strickland, Deborah Forst, Joana L. Mora, Nancy Wang, Maura Mahar, Jorg Dietrich, Elizabeth R. Gerstner, April F. Eichler, Eudocia Q. Lee, Justine V. Cohen, Dejan Juric, Priscilla K. Brastianos, Michael White, Anita Giobbie-Hurder, Naema Nayyar, Helen A. Shih, Kevin S. Oh, Ryan J. Sullivan, Ibiayi Dagogo-Jack, Nan Lin, Aditya Bardia |
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| Rok vydání: | 2021 |
| Předmět: |
Adult
Male medicine.medical_specialty Fever Cancer therapy Science General Physics and Astronomy Phases of clinical research Ipilimumab Article General Biochemistry Genetics and Molecular Biology Hepatitis Metastasis Antineoplastic Agents Immunological Median follow-up Internal medicine Antineoplastic Combined Chemotherapy Protocols Meningeal Neoplasms medicine Clinical endpoint Humans Adverse effect Fatigue Survival analysis Aged Multidisciplinary Brain Neoplasms business.industry Nausea General Chemistry Exanthema Middle Aged Colitis Survival Analysis Rash Anorexia Nivolumab Tumour immunology Female Immunotherapy medicine.symptom business Meningeal Carcinomatosis medicine.drug |
| Zdroj: | Nature Communications, Vol 12, Iss 1, Pp 1-7 (2021) Nature Communications |
| ISSN: | 2041-1723 |
| Popis: | Leptomeningeal disease (LMD) is a common complication from solid tumor malignancies with a poor prognosis and limited treatment options. We present a single arm Phase II study of 18 patients with LMD receiving combined ipilimumab and nivolumab until progression or unacceptable toxicity (NCT02939300). The primary end point is overall survival at 3 months (OS3). Secondary end points include toxicity, cumulative time-to-progression at 3 months, and progression-free survival. A Simon two-stage design is used to compare a null hypothesis OS3 of 18% against an alternative of 44%. Median follow up based on patients still alive is 8.0 months (range: 0.5 to 15.9 months). The study has met its primary endpoint as 8 of 18 (OS3 0.44; 90% CI: 0.24 to 0.66) patients are alive at three months. One third of patients have experienced one (or more) grade-3 or higher adverse events. Two patients have discontinued protocol treatment due to unacceptable toxicity (hepatitis and colitis, respectively). The most frequent adverse events include fatigue (N = 7), nausea (N = 6), fever (N = 6), anorexia (N = 6) and rash (N = 6). Combined ipilimumab and nivolumab has an acceptable safety profile and demonstrates promising activity in LMD patients. Larger, multicenter clinical trials are needed to validate these results. Leptomeningeal metastases from solid tumors are a rare complication with a very poor prognosis. Here the authors report the efficacy and safety of combined ipilimumab and nivolumab in patients with leptomeningeal carcinomatosis. |
| Databáze: | OpenAIRE |
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