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Record W4321436832 · doi:10.1200/jco.22.01989

Pembrolizumab Plus Pemetrexed and Platinum in Nonsquamous Non–Small-Cell Lung Cancer: 5-Year Outcomes From the Phase 3 KEYNOTE-189 Study

2023· article· en· W4321436832 on OpenAlexaff
Marina Chiara Garassino, Shirish M. Gadgeel, Giovanna Speranza, Enriqueta Felip, Emilio Esteban, Manuel Dómine, Maximilian J. Hochmair, Steven Powell, Helge Bischoff, Nir Peled, Francesco Grossi, Ross Jennens, Martin Reck, Rina Hui, Edward B. Garon, Takayasu Kurata, Jhanelle E. Gray, Paul Schwarzenberger, Erin Jensen, M. Catherine Pietanza, Delvys Rodríguez‐Abreu

Bibliographic record

VenueJournal of Clinical Oncology · 2023
Typearticle
Languageen
FieldMedicine
TopicCancer Immunotherapy and Biomarkers
Canadian institutionsHôpital Charles-Le Moyne
FundersChugai PharmaceuticalEMD SeronoGenentechIpsenEli Lilly and CompanyOno PharmaceuticalAstellas PharmaEisaiRegeneron PharmaceuticalsNateraGrifolsY-mAbs TherapeuticsShionogiActuate TherapeuticsDaiichi Sankyo EuropeGilead SciencesCalithera BiosciencesPfizerIncyteMirati TherapeuticsLes Laboratories Pierre FabreHelsinnMerck KGaASanofiGlaxoSmithKlineHelsinn TherapeuticsAmgenCelgeneAstraZenecaSamsungBristol-Myers Squibb
KeywordsPemetrexedMedicinePembrolizumabCarboplatinInternal medicineLung cancerOncologyClinical endpointHazard ratioPhases of clinical researchClinical trialSurgeryCisplatinChemotherapyCancerConfidence intervalImmunotherapy

Abstract

fetched live from OpenAlex

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically on the based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported. We present 5-year outcomes from the phase 3 KEYNOTE-189 study (ClinicalTrials.gov identifier: NCT02578680 ). Eligible patients with previously untreated metastatic nonsquamous non–small-cell lung cancer without EGFR/ALK alterations were randomly assigned 2:1 to pembrolizumab 200 mg or placebo once every 3 weeks for up to 35 cycles with pemetrexed and investigator's choice of carboplatin/cisplatin for four cycles, followed by maintenance pemetrexed until disease progression or unacceptable toxicity. Primary end points were overall survival (OS) and progression-free survival (PFS). Among 616 randomly assigned patients (n = 410, pembrolizumab plus pemetrexed-platinum; n = 206, placebo plus pemetrexed-platinum), median time from random assignment to data cutoff (March 8, 2022) was 64.6 (range, 60.1-72.4) months. Hazard ratio (95% CI) for OS was 0.60 (0.50 to 0.72) and PFS was 0.50 (0.42 to 0.60) for pembrolizumab plus platinum-pemetrexed versus placebo plus platinum-pemetrexed. 5-year OS rates were 19.4% versus 11.3%. Toxicity was manageable. Among 57 patients who completed 35 cycles of pembrolizumab, objective response rate was 86.0% and 3-year OS rate after completing 35 cycles (approximately 5 years after random assignment) was 71.9%. Pembrolizumab plus pemetrexed-platinum maintained OS and PFS benefits versus placebo plus pemetrexed-platinum, regardless of programmed cell death ligand-1 expression. These data continue to support pembrolizumab plus pemetrexed-platinum as a standard of care in previously untreated metastatic non–small-cell lung cancer without EGFR/ALK alterations.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.008
metaresearch head score (Gemma)0.004
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Randomized trial · Consensus signal: Randomized trial
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.008
Threshold uncertainty score0.044

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0080.004
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0010.003
Bibliometrics0.0000.001
Science and technology studies0.0000.000
Scholarly communication0.0010.001
Open science0.0010.001
Research integrity0.0010.003
Insufficient payload (model declined to judge)0.0030.001

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.115
GPT teacher head0.474
Teacher spread0.359 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designRandomized trial
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations643
Published2023
Admission routes1
Has abstractyes

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