Evidence map›Paper›PMID 40334315›Full record

Trial reportESMO open2025

Durvalumab with or without tremelimumab in combination with chemotherapy in first-line metastatic non-small-cell lung cancer: outcomes by tumor mutational burden in POSEIDON.

S Peters, K S Oliner, A L'Hernault, M Ratcliffe, H Madison, Z Lai, R Stewart, H Mann, C Lowery, E B Garon and 2 more

Abstract readRandomized Controlled TrialClinical Trial, Phase III
In one paragraph

Trial report in ESMO open, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Review
  2. Article
  3. Review
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.

S PetersCentre Hospitalier Universitaire Vaudois, Lausanne University, Lausanne, Switzerland. Electronic address: Solange.Peters@chuv.ch.
K S OlinerAstraZeneca, Gaithersburg, USA.
A L'HernaultAstraZeneca, Cambridge, UK.
M RatcliffeAstraZeneca, Cambridge, UK.
H MadisonAstraZeneca, Gaithersburg, USA.
Z LaiAstraZeneca, Waltham, USA.
R StewartAstraZeneca, Cambridge, UK.
H MannAstraZeneca, Cambridge, UK.
C LoweryAstraZeneca, Gaithersburg, USA.
E B GaronDavid Geffen School of Medicine at UCLA, Los Angeles, USA.
T MokState Key Laboratory of Translational Oncology, Department of Clinical Oncology, Chinese University of Hong Kong, Hong Kong, China.
M L JohnsonSarah Cannon Research Institute, SCRI Oncology Partners, Nashville, USA.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundIn updated analyses from the phase III POSEIDON study, after a median follow-up of >5 years, tremelimumab plus durvalumab and chemotherapy (T + D + CT) showed durable long-term overall survival (OS) benefit versus CT alone in first-line metastatic non-small-cell lung cancer (mNSCLC). In this article, we report the associations of tumor mutational burden (TMB) with outcomes of D with or without T in combination with CT versus CT alone. PATIENTS AND

methodsA total of 1013 patients with EGFR/ALK wild-type mNSCLC were randomized (1 : 1 : 1) to T + D + CT, D + CT, or CT, stratified by programmed cell death-ligand 1 (PD-L1) tumor cell (TC) expression ≥50% versus <50%, disease stage (IVA versus IVB) and histology (squamous versus nonsquamous). Patient subgroups were defined by a range of blood TMB (bTMB) values, including at a prespecified cut-off of 20 mutations (mut)/megabase (Mb) and across further subdivisions by PD-L1 TC expression ≥1% or <1% and by tissue TMB (tTMB) values.

resultsAt the primary OS data cut-off (12 March 2021), at each bTMB or tTMB cut-off, the magnitude of OS benefit appeared greater among patients in the bTMB- or tTMB-high subgroups for the T + D + CT arm versus the CT arm but was similar between subgroups for the D + CT arm versus the CT arm. Updated OS analyses in the bTMB ≥20 and <20 mut/Mb subgroups, after median follow-up of >5 years (data cut-off 24 August 2023), were similar to those obtained at the primary OS data cut-off.

conclusionsFirst-line treatment with T (limited course) plus D (until progression) and four cycles of CT consistently improved clinical outcomes versus CT alone in both bTMB-high and -low subgroups, and also in both high and low tTMB subgroups, in patients with mNSCLC. Benefit appeared greater in the TMB-high versus TMB-low subgroups; the addition of anti-cytotoxic T lymphocyte-associated antigen-4 to anti-PD-L1 and CT seemed to increase the magnitude of this difference.

Indexed as

Antibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsCarcinoma, Non-Small-Cell LungLung NeoplasmsAdultAgedFemaleHumansMaleMiddle AgedMutationTreatment OutcomeAntibodies, MonoclonalAntibodies, Monoclonal, Humanizeddurvalumabtremelimumabdurvalumabnon-small-cell lung cancerPOSEIDONtremelimumabtumor mutational burden

Identifiers

PMID40334315
PMCPMC12167883

What OpenQuestion holds

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Registered trials

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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.