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Dostarlimab for primary advanced or recurrent (A/R) endometrial cancer (EC): Outcomes by blinded independent central review (BICR) of the RUBY trial (ENGOT-EN6-NSGO/GOG-3031/RUBY).

2023· article· en· W4379333138 on OpenAlexaff
Matthew A. Powell, Sakari Hietanen, Robert L. Coleman, Bradley J. Monk, Oleksandr Zub, David M. O’Malley, Lucy Gilbert, Iwona Podzielinski, Roberto Angioli, Dana M. Chase, Dirk Bauerschlag, Destin Black, A.M. Thijs, Sudarshan Sharma, Michael A. Gold, Kari L. Ring, Zangdong He, Shadi Stevens, Brian M. Slomovitz, Mansoor Raza Mirza

Bibliographic record

VenueJournal of Clinical Oncology · 2023
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicCancer Genomics and Diagnostics
Canadian institutionsMcGill University Health Centre
Fundersnot available
KeywordsMedicineClinical endpointInternal medicineCarboplatinEndometrial cancerMicrosatellite instabilityOncologyPaclitaxelPlaceboRandomized controlled trialProgression-free survivalCancerOverall survivalGynecologyChemotherapyCisplatinPathology

Abstract

fetched live from OpenAlex

5503 Background: RUBY (NCT03981796) evaluated the efficacy and safety of the anti–programmed death 1 (PD-1) dostarlimab + standard of care (SOC) carboplatin paclitaxel (CP) versus CP alone in A/R EC. The primary endpoint of PFS by investigator assessment (INV) per RECIST v1.1 was significantly longer with dostarlimab+CP than placebo (PBO)+CP in the mismatch repair deficient/microsatellite instability-high (dMMR/MSI-H; HR 0.28; 95% CI 0.162–0.495) and overall populations (HR 0.64, 95% CI 0.507–0.800). Here we present secondary efficacy endpoints by BICR. Methods: RUBY is a phase 3, global, randomized, double-blind, multicenter, PBO-controlled study. Patients (pts) with primary advanced stage III or IV or first recurrent EC were randomized 1:1 to receive dostarlimab 500 mg, or PBO, plus carboplatin AUC 5 and paclitaxel 175 mg/m2 Q3W (6 cycles), followed by dostarlimab 1000 mg, or PBO, monotherapy Q6W for up to 3 y. Secondary endpoints by BICR assessment per RECIST v1.1 were PFS, ORR, DOR, and DCR in the overall and dMMR/MSI-H populations. Results: 494 pts were randomized (245:dostarlimab+CP; 249:PBO+CP); 47.8% had recurrent disease, 18.6% and 33.6% had primary stage III and IV disease, respectively. PFS by BICR was longer with dostarlimab+CP than PBO+CP in the dMMR/MSI-H (HR 0.29; 95% CI 0.158–0.543) and overall populations (HR 0.66; 95% CI 0.517–0.853; Table). Consistent benefits were seen with dostarlimab+CP for ORR, DCR, and DOR by BICR in the dMMR/MSI-H and overall populations (Table). Safety was previously reported. Conclusions: Dostarlimab+CP showed clinically meaningful improvement in BICR-assessed PFS in the dMMR/MSI-H and overall populations compared with CP alone. The HRs for PFS per BICR and per INV were consistent, which supports the reliability of PFS by INV in EC trials. Benefits were seen in all BICR-assessed endpoints, which were consistent with INV. Dostarlimab+CP represents a new SOC for pts with primary A/R EC. Clinical trial information: NCT03981796 . [Table: see text]

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)0.016
metaresearch head score (Gemma)0.011
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 score0.016
Threshold uncertainty score0.086

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0160.011
Meta-epidemiology (narrow)0.0010.001
Meta-epidemiology (broad)0.0030.002
Bibliometrics0.0010.001
Science and technology studies0.0010.001
Scholarly communication0.0010.001
Open science0.0010.001
Research integrity0.0020.001
Insufficient payload (model declined to judge)0.0050.001

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 head0.467
Teacher spread0.353 · 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

Citations3
Published2023
Admission routes1
Has abstractyes

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