TY - JOUR
T1 - In Patients with Melanoma Brain Metastases, Is Combination Immune Checkpoint Inhibition a Safe and Effective First-Line Treatment? A Critically Appraised Topic
AU - Gritsch, David
AU - Mrugala, Maciej M.
AU - Marks, Lisa A.
AU - Wingerchuk, Dean M.
AU - O'Carroll, Cumara B.
N1 - Publisher Copyright:
© 2022 Lippincott Williams and Wilkins. All rights reserved.
PY - 2022/9/12
Y1 - 2022/9/12
N2 - Background: Combined PD-1/PD-L1 and CTLA-4 immune checkpoint inhibition for the has been shown to produce superior results in the treatment of malignant melanoma when compared to monotherapy. However, patients with intracranial disease were excluded from these studies given their poor prognosis. Objective: The objective of this study was to critically assess current evidence supporting the co-administration of PD-1/PD-L1 and CTLA-4 inhibitors in the treatment of melanoma brain metastases. Methods: The objective was addressed through the development of a critically appraised topic that included a clinical scenario, structured question, literature search strategy, critical appraisal, assessment of results, evidence summary, commentary, and bottom-line conclusions. Participants included consultant and resident neurologists, a medical librarian, clinical epidemiologists, and a content expert in the field of neuro-oncology. Results: A recent, open-label, non-comparative randomized phase II trial was selected for critical appraisal. This trial evaluated the efficacy and safety of nivolumab alone or in combination with ipilimumab in 79 adult patients with untreated, asymptomatic melanoma brain metastases. The rates of the primary outcome (intracranial response at ≥12 wk) in the primary endpoint cohort were 46% for cohort A (combination therapy) and 20% for cohort B (nivolumab monotherapy). No treatment related deaths were observed in the study. Grade 4 adverse events occurred in 9% of patients in cohort A and none in cohort B. Conclusions: Co-administration of ipilimumab and nivolumab as first-line therapy is effective in the treatment of asymptomatic melanoma brain metastases, with an acceptable safety profile.
AB - Background: Combined PD-1/PD-L1 and CTLA-4 immune checkpoint inhibition for the has been shown to produce superior results in the treatment of malignant melanoma when compared to monotherapy. However, patients with intracranial disease were excluded from these studies given their poor prognosis. Objective: The objective of this study was to critically assess current evidence supporting the co-administration of PD-1/PD-L1 and CTLA-4 inhibitors in the treatment of melanoma brain metastases. Methods: The objective was addressed through the development of a critically appraised topic that included a clinical scenario, structured question, literature search strategy, critical appraisal, assessment of results, evidence summary, commentary, and bottom-line conclusions. Participants included consultant and resident neurologists, a medical librarian, clinical epidemiologists, and a content expert in the field of neuro-oncology. Results: A recent, open-label, non-comparative randomized phase II trial was selected for critical appraisal. This trial evaluated the efficacy and safety of nivolumab alone or in combination with ipilimumab in 79 adult patients with untreated, asymptomatic melanoma brain metastases. The rates of the primary outcome (intracranial response at ≥12 wk) in the primary endpoint cohort were 46% for cohort A (combination therapy) and 20% for cohort B (nivolumab monotherapy). No treatment related deaths were observed in the study. Grade 4 adverse events occurred in 9% of patients in cohort A and none in cohort B. Conclusions: Co-administration of ipilimumab and nivolumab as first-line therapy is effective in the treatment of asymptomatic melanoma brain metastases, with an acceptable safety profile.
KW - brain metastases
KW - checkpoint inhibitors
KW - immunotherapy
KW - ipilimumab
KW - malignant melanoma
KW - nivolumab
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UR - http://www.scopus.com/inward/citedby.url?scp=85137163394&partnerID=8YFLogxK
U2 - 10.1097/NRL.0000000000000439
DO - 10.1097/NRL.0000000000000439
M3 - Article
C2 - 35834790
AN - SCOPUS:85137163394
SN - 1074-7931
VL - 27
SP - 290
EP - 297
JO - Neurologist
JF - Neurologist
IS - 5
ER -