Evidence map›Paper›PMID 41677907›Full record

SynthesisCancer immunology, immunotherapy : CII2026

First-line ipilimumab plus nivolumab in advanced merkel cell carcinoma: a meta-analysis of prospective trials and real-world validation cohort.

Tanya Ramadoss, Christian Palacios, Matthew Nichols, Zeynep Eroglu, Joseph Markowitz, Lilit Karapetyan, Ahmad A Tarhini, Evan J Wuthrick, Vernon K Sondak, Kenneth Y Tsai and 2 more

Abstract readMeta-AnalysisSystematic Review
In one paragraph

Synthesis in Cancer immunology, immunotherapy : CII, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors.

Tanya RamadossNova Southeastern University Dr. Kiran C. Patel College of Allopathic Medicine, Davie, FL, USA.
Christian PalaciosNova Southeastern University Dr. Kiran C. Patel College of Allopathic Medicine, Davie, FL, USA.
Matthew NicholsDepartment of Cutaneous Oncology, Moffitt Cancer Center, Tampa, FL, USA.
Zeynep ErogluDepartment of Cutaneous Oncology, Moffitt Cancer Center, Tampa, FL, USA.
Joseph MarkowitzDepartment of Cutaneous Oncology, Moffitt Cancer Center, Tampa, FL, USA.
Lilit KarapetyanDepartment of Cutaneous Oncology, Moffitt Cancer Center, Tampa, FL, USA.
Ahmad A TarhiniDepartment of Cutaneous Oncology, Moffitt Cancer Center, Tampa, FL, USA.
Evan J WuthrickDepartment of Radiation Oncology, Moffitt Cancer Center, Tampa, FL, USA.
Vernon K SondakDepartment of Cutaneous Oncology, Moffitt Cancer Center, Tampa, FL, USA.
Kenneth Y TsaiDepartment of Anatomic Pathology, Moffitt Cancer Center, Tampa, FL, USA.
Nikhil I KhushalaniDepartment of Cutaneous Oncology, Moffitt Cancer Center, Tampa, FL, USA.
Andrew S BrohlDepartment of Cutaneous Oncology, Moffitt Cancer Center, Tampa, FL, USA. andrew.brohl@moffitt.org.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundAdvanced Merkel cell carcinoma (MCC) has a high response rate to immune checkpoint blockade (ICB). While early phase studies have demonstrated activity of dual ICB with anti-PD-1 plus anti-CTLA-4 agents in both the first- and second-line settings, the role of combination therapy as a first-line approach remains controversial.

methodsWe conducted a systematic review and meta-analysis to summarize the current evidence of first-line ICB therapy in MCC and to compare the pooled objective response rate (ORR) between combination ICB and monotherapy. Pooled ORRs were estimated using fixed-effects meta-analyses, and these results were statistically compared between combination ICB and monotherapy. In addition to the meta-analysis and as real-world validation, we performed a retrospective chart review of MCC patients treated with first-line combination ICB at a single referral center.

resultsIn the meta-analysis, the pooled ORR of ipilimumab plus nivolumab was significantly higher than that of either anti-PD(L)1 monotherapy when considering all anti-PD-1 and anti-PD-L1 agents (81.0% vs. 49.6%, p = 0.0001) as well as monotherapy when restricted to anti-PD-1 agents (81.0% vs. 57.0%, p = 0.0043). Concordant with pooled trial findings, we identified eight patients treated off protocol with first-line combination ICB at our institution, with seven (87.5%) achieving objective response. DISCUSSION: Based on meta-analysis of clinical trial data, first-line treatment of advanced Merkel cell carcinoma with ipilimumab plus nivolumab results in a higher objective response rate compared to monotherapy. The clinical decision to select combination therapy over monotherapy must weigh this response rate benefit with the unknown survival benefit and higher toxicity.

Indexed as

Antineoplastic Combined Chemotherapy ProtocolsCarcinoma, Merkel CellIpilimumabNivolumabSkin NeoplasmsHumansImmune Checkpoint InhibitorsProspective StudiesImmune Checkpoint InhibitorsIpilimumabNivolumabCheckpoint inhibitorImmunotherapyIpilimumabMerkel cell carcinomaNivolumab

Identifiers

PMID41677907
PMCPMC12900986

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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Registered trials

None linked

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 Socratic graph.