Association Between Immune-Related Adverse Events and Recurrence-Free Survival Among Patients With Stage III Melanoma Randomized to Receive Pembrolizumab or Placebo

Why is this work in the frame?

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

Full frame distilled prediction

Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

Candidate categories

none

Consensus categories

none

Domain

Candidate signal: noneConsensus signal: none

Study design

Candidate signal: Randomized trialConsensus signal: none

Genre

Candidate signal: EmpiricalConsensus signal: Empirical

Teacher disagreement score

0.154

Threshold uncertainty score

0.685

Validation status

machine_predicted_unvalidated · codex-gemma-dda1882f352a

Codex and Gemma teacher scores by category

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.

Teacher spread

0.256 · how far apart the two teachers sit on this one work

Validation status

score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Abstract

Importance: Whether immune-related adverse events (irAEs) indicate drug activity in patients treated with immune checkpoint inhibitors remains unknown. Objective: To investigate the association between irAEs and recurrence-free survival (RFS) in the double-blind EORTC 1325/KEYNOTE-054 clinical trial comparing pembrolizumab therapy and placebo for the treatment of patients with high-risk stage III melanoma. Design, Setting, and Participants: A total of 1019 adults with stage III melanoma were randomly assigned on a 1:1 ratio to receive treatment with pembrolizumab therapy or placebo. Eligible patients were adults 18 years and older with complete resection of cutaneous melanoma metastatic to lymph nodes, classified with stage IIIA (at least 1 micrometastasis measuring >1 mm in greatest diameter), IIIB, or IIIC (without in-transit metastasis) cancer. Patients were randomized from August 26, 2015, to November 14, 2016. The clinical cutoff for the data set was October 2, 2017. Analyses were then performed on the database, which was locked on November 28, 2017. Interventions: Participants were scheduled to receive 200 mg of pembrolizumab or placebo every 3 weeks for a total of 18 doses for approximately 1 year or until disease recurrence, unacceptable toxic effects, major protocol violation, or withdrawal of consent. Main Outcomes and Measures: The association between irAEs and RFS was estimated using a Cox model adjusted for sex, age, and AJCC-7 stage, with a time-varying covariate that had a value of 0 before irAE onset and 1 after irAE onset. Results: Of 1011 patients who began treatment with pembrolizumab therapy or placebo, 622 (61.5%) were men and 389 (38.5%) were women; 386 patients (38.2%) were aged 50 to 64 years, 377 (37.3%) were younger than 50 years, and 248 (24.5%) were 65 years and older. Consistent with the reported main analysis in the intent-to-treat population, RFS was longer in the pembrolizumab arm compared with the placebo arm (hazard ratio [HR], 0.56; 98.4% CI, 0.43-0.74) among patients who started treatment. The incidence of irAEs was 190 (37.4%) in the pembrolizumab arm (n = 509) and 45 (9.0%) in the placebo arm (n = 502); in each treatment group, the incidence was similar for men and women. The occurrence of an irAE was associated with a longer RFS in the pembrolizumab arm (HR, 0.61; 95% CI, 0.39-0.95; P = .03) in both men and women. However, in the placebo arm, this association was not significant. Compared with the placebo arm, the reduction in the hazard of recurrence or death in the pembrolizumab arm was greater after the onset of an irAE than without or before an irAE (HR, 0.37; 95% CI, 0.24-0.57 vs HR, 0.61; 95% CI, 0.49-0.77, respectively; P = .03). Conclusions and Relevance: In this study, the occurrence of an irAE was associated with a longer RFS in the pembrolizumab arm. Trial Registrations: ClinicalTrials.gov identifier: NCT02362594; EudraCT identifier: 2014-004944-37.

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.

The record

Venue

JAMA Oncology

Topic

Cancer Immunotherapy and Biomarkers

Field

Medicine

Canadian institutions

Centre Hospitalier de l’Université de Montréal

Funders

PharmacyclicsGenentechMerck CanadaDeutschen Konsortium für Translationale KrebsforschungRadboud Universitair Medisch CentrumMelanoma Institute AustraliaAmgenRadboud UniversiteitUniversitat de BarcelonaAstellas PharmaLes Laboratories Pierre FabreEuropean Organisation for Research and Treatment of CancerSkylineDxSun PharmaPeter MacCallum Cancer CentreSyndax PharmaceuticalsRegeneron PharmaceuticalsEndocyteArray BioPharmaAix-Marseille UniversitéInflaRxPfizerIncyteF. Hoffmann-La RocheSanofiGlaxoSmithKlineNeraCareUniversity of SydneyMedizinischen Hochschule HannoverAstraZenecaEli Lilly and CompanyBristol-Myers Squibb

Keywords

MedicinePembrolizumabInternal medicineAdverse effectPlaceboRandomized controlled trialClinical trialMelanomaOncologySurgeryCancerImmunotherapyPathology

Has abstract in OpenAlex

yes

API

/api/v1/works/W2997720498