Evidence map›Paper›PMID 33880555›Full record

ArticleNeuro-oncology2021

Safety and efficacy of the combination of nivolumab plus ipilimumab in patients with melanoma and asymptomatic or symptomatic brain metastases (CheckMate 204).

Hussein A Tawbi, Peter A Forsyth, F Stephen Hodi, Christopher D Lao, Stergios J Moschos, Omid Hamid, Michael B Atkins, Karl Lewis, Reena P Thomas, John A Glaspy and 13 more

Registry-linked trialOpen access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Neuro-oncology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02320058 (A Multi-Center Phase 2 Open-Label Study to Evaluate Safety and Efficacy in Subjects With Melanoma Metastatic to the Brain Treated With Nivolumab in Combination With Ipilimumab Followed by Nivolumab Monotherapy), which is not on this map. Cited by 63 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
63citing papers in PubMed, 2 pooled it
19.2field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT02320058 phase2completednot on this map

A Multi-Center Phase 2 Open-Label Study to Evaluate Safety and Efficacy in Subjects With Melanoma Metastatic to the Brain Treated With Nivolumab in Combination With Ipilimumab Followed by Nivolumab Monotherapy

TypeinterventionalSponsorBristol-Myers SquibbRan2015 to 2020Enrolled119ConditionsMelanomaArmsIpilimumab, Nivolumab
3 · Its place in the literature

Who cites it

63 citing papers in PubMed, 2 syntheses or guidelines pooled it, 122 citations in OpenAlex.

  1. Guideline
  2. SEOM-GEINO clinical guideline of systemic therapy and management of brain central nervous system metastases (2021).Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2022
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3 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

23 authors at 20 institutions in 1 country.

Hussein A TawbiDepartment of Melanoma Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.ORCID 0000-0003-1942-851X
Peter A ForsythDepartment of Neuro-Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida, USA.
F Stephen HodiDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
Christopher D LaoDepartment of Dermatology, University of Michigan, Ann Arbor, Michigan, USA.
Stergios J MoschosDivision of Hematology and Oncology, The University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill, North Carolina, USA.
Omid HamidDepartment of Translational Research & Immunotherapy, The Angeles Clinic and Research Institute, A Cedars-Sinai Affiliate, Los Angeles, California, USA.
Michael B AtkinsDepartment of Medical Oncology, Georgetown Lombardi Comprehensive Cancer Center, Washington, DC, USA.ORCID 0000-0003-3901-9924
Karl LewisDepartment of Medical Oncology, University of Colorado Comprehensive Cancer Center, Aurora, Colorado, USA.
Reena P ThomasDepartment of Neurology, Stanford University Cancer Center, Stanford, California, USA.
John A GlaspyDepartment of Medicine, Jonsson Comprehensive Cancer Center, University of California, Los Angeles, California, USA.
Sekwon JangDepartment of Medicine, Inova Schar Cancer Institute, Virginia Commonwealth University, Fairfax, Virginia, USA.
Alain P AlgaziDepartment of Hematology and Oncology, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, California, USA.
Nikhil I KhushalaniDepartment of Cutaneous Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida, USA.
Michael A PostowDepartment of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
Anna C PavlickDepartment of Medical Oncology, Weill Cornell Medicine, New York, New York, USA.
Marc S ErnstoffDepartment of Immuno-Oncology, Division of Cancer Treatment and Diagnosis, National Cancer Institute at the National Institutes of Health, Rockville, Maryland, USA.
David A ReardonCenter for Neuro-Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
Igor PuzanovDepartment of Medical Oncology, Roswell Park Cancer Institute, Buffalo, New York, USA.
Ragini R KudchadkarDepartment of Hematology and Medical Oncology, Winship Cancer Institute of Emory University, Atlanta, Georgia, USA.
Ahmad A TarhiniDepartment of Cutaneous Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida, USA.
Anne SumbulBiostatistics, Bristol Myers Squibb, Princeton, New Jersey, USA.
Jasmine I RizzoOncology Clinical Development, Bristol Myers Squibb, Princeton, New Jersey, USA.
Kim A MargolinDepartment of Medical Oncology, City of Hope, Duarte, California, USA.
Moffitt Cancer Center · USBristol-Myers Squibb (United States) · USAngeles Clinic and Research Institute · USCenter for Neuro-Oncology · USCity Of Hope National Medical Center · USCornell University · USDana-Farber Cancer Institute · USEmory University · USGeorgetown University Medical Center · USMemorial Sloan Kettering Cancer Center · USNational Institutes of Health · USRoswell Park Comprehensive Cancer Center · USStanford University · USThe University of Texas MD Anderson Cancer Center · USUniversity of California, Los Angeles · USUniversity of California, San Francisco · USUniversity of Colorado Cancer Center · USUniversity of Michigan · USUniversity of North Carolina at Chapel Hill · USVirginia Commonwealth University · US

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Hongbiao Carl Lekaye · 1985 to 2026
$347.4M
NCI NIH HHS P30 CA008748
6 · The paper itself

Abstract

backgroundIn patients with melanoma and asymptomatic brain metastases (MBM), nivolumab plus ipilimumab provided an intracranial response rate of 55%. Here, we present the first report for patients who were symptomatic and/or required corticosteroids and updated data for asymptomatic patients.

methodsPatients with measurable MBM, 0.5-3.0 cm, were enrolled into Cohort A (asymptomatic) or Cohort B (stable neurologic symptoms and/or receiving corticosteroids). Nivolumab, 1 mg/kg, and ipilimumab, 3 mg/kg, were given intravenously every 3 weeks ×4, followed by nivolumab, 3 mg/kg, every 2 weeks until progression, unacceptable toxicity, or 24 months. The primary endpoint was intracranial clinical benefit rate (CBR; complete response [CR], partial response [PR], or stable disease ≥6 months).

resultsSymptomatic patients (N = 18) received a median of one nivolumab and ipilimumab combination dose and had an intracranial CBR of 22.2%. Two of 12 patients on corticosteroids had CR; 2 responded among the 6 not on corticosteroids. Median intracranial progression-free survival (PFS) and overall survival (OS) were 1.2 and 8.7 months, respectively. In contrast, with 20.6 months of follow-up, we confirmed an intracranial CBR of 58.4% in asymptomatic patients (N = 101); median duration of response, PFS, and OS were not reached. No new safety signals were observed.

conclusionsNivolumab plus ipilimumab provides durable clinical benefit for asymptomatic patients with MBM and should be considered for first-line therapy. This regimen has limited activity in MBM patients with neurologic symptoms and/or requiring corticosteroids, supporting the need for alternative approaches and methods to reduce the dependency on corticosteroids. Clinical trial registration. ClinicalTrials.gov, NCT02320058.

Indexed as

Brain NeoplasmsMelanomaAntineoplastic Combined Chemotherapy ProtocolsHumansIpilimumabNivolumabIpilimumabNivolumabcheckpoint inhibitoripilimumabmelanomanivolumabsymptomatic brain metastases

Identifiers

PMID33880555
PMCPMC8563325
OpenAlexW3155601180

What OpenQuestion holds

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.