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KEYNOTE-204: Randomized, open-label, phase III study of pembrolizumab (pembro) versus brentuximab vedotin (BV) in relapsed or refractory classic Hodgkin lymphoma (R/R cHL).

2020· article· en· W3029806582 on OpenAlexaff
John Kuruvilla, Radhakrishnan Ramchandren, Armando Santoro, Ewa Paszkiewicz‐Kozik, Robin Gasiorowski, Nathalie A. Johnson, В Я Мельниченко, Laura Maria Fogliatto, Iara Gonçalves, José de Lima Oliveira, Valéria Buccheri, Guilherme Fleury Perini, Neta Goldschmidt, Sergey Alekseev, Iryna Kryachok, Naohiro Sekiguchi, Ying Zhu, Akash Nahar, Patricia Marinello, Pier Luigi Zinzani

Bibliographic record

VenueJournal of Clinical Oncology · 2020
Typearticle
Languageen
FieldMedicine
TopicLymphoma Diagnosis and Treatment
Canadian institutionsJewish General HospitalPrincess Margaret Cancer Centre
Fundersnot available
KeywordsMedicineBrentuximab vedotinInternal medicinePembrolizumabOncologyRefractory (planetary science)LymphomaHodgkin lymphomaCancerImmunotherapy

Abstract

fetched live from OpenAlex

8005 Background: PD-1 blockade via pembro monotherapy showed antitumor activity in R/R cHL. KEYNOTE-204 (NCT02684292) was a randomized, international, open-label, phase III study of pembro vs BV in R/R cHL. Methods: Patients (pts) were aged ≥18 y, were post−autologous stem cell transplant (auto-SCT) or ineligible for auto-SCT, and had measurable disease and ECOG PS 0 or 1. BV-naive and BV-exposed pts were eligible. Pts were randomized 1:1 to pembro 200 mg IV Q3W or BV 1.8 mg/kg IV Q3W and stratified by prior auto-SCT (yes vs no) and status after 1L therapy (primary refractory vs relapsed <12 mo vs relapsed ≥12 mo after end of 1L therapy). Primary end points: PFS by blinded independent central review (BICR) per International Working Group (IWG) criteria including clinical and imaging data after auto-SCT or allogeneic SCT (allo-SCT) and OS. Key secondary end points: PFS excluding clinical and imaging data after auto-SCT or allo-SCT (PFS-secondary), and ORR by BICR per IWG, PFS by investigator review per IWG, and safety. Exploratory end point: DOR by BICR per IWG. Results: 304 pts were randomized and 300 were treated (148, pembro; 152, BV); 256 discontinued. Median (range) follow-up: 24.7 (0.6-42.3) mo. 15 pts were BV exposed. Median (range) time on treatment was 305.0 (1-814) and 146.5 (1-794) days with pembro and BV, respectively. Statistically significant improvement was observed with pembro vs BV for primary PFS analysis (HR 0.65 [95% CI 0.48-0.88; P =0.00271]; median 13.2 vs 8.3 mo); 12-mo PFS rates were 53.9% vs 35.6%, respectively. Benefit was observed in all subgroups tested, including pts with no auto-SCT (HR=0.61), primary refractory disease (HR=0.52), prior BV (HR=0.34) and BV naive (HR=0.67). Significant improvement in PFS-secondary was observed with pembro vs BV (HR 0.62 [95% CI 0.46-0.85]; median 12.6 vs 8.2 mo). Per investigator assessment, PFS was longer with pembro vs BV (HR 0.49 [95% CI 0.36-0.67]; median 19.2 vs 8.2 mo). ORR was 65.6% for pembro and 54.2% for BV; CR rates were 24.5% and 24.2%, respectively. Median (range) DOR was 20.7 mo (0.0+ to 33.2+) for pembro and 13.8 mo (0.0+ to 33.9+) for BV. Grade 3-5 TRAEs: 19.6% of pts with pembro and 25.0% with BV. One death due to TRAE occurred with pembro (pneumonia). Conclusions: In pts with R/R cHL, pembro was superior to BV and demonstrated statistically significant and clinically meaningful improvement in PFS across all subgroups, with safety consistent with previous reports. Pembro monotherapy should be standard of care for this pt population with R/R/cHL. Clinical trial information: NCT02684292 .

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)0.002
metaresearch head score (Gemma)0.002
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 score0.011
Threshold uncertainty score0.036

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0020.002
Meta-epidemiology (narrow)0.0020.001
Meta-epidemiology (broad)0.0020.001
Bibliometrics0.0000.000
Science and technology studies0.0000.001
Scholarly communication0.0010.001
Open science0.0010.001
Research integrity0.0020.004
Insufficient payload (model declined to judge)0.0110.002

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 head0.254
GPT teacher head0.501
Teacher spread0.247 · 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".

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Citations34
Published2020
Admission routes1
Has abstractyes

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