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Antitumor activity and safety of pembrolizumab in patients with advanced recurrent ovarian cancer: Interim results from the phase 2 KEYNOTE-100 study.

2018· article· en· W3001160691 on OpenAlexaff
Ursula A. Matulonis, Ronnie Shapira‐Frommer, Alessandro D. Santin, Alla Sergeevua Lisyanskaya, Sandro Pignata, Ignace Vergote, Francesco Raspagliesi, Gabe S. Sonke, Michael J. Birrer, Diane Provencher, Jalid Sehouli, Nicoletta Colombo, Antonio González-Martı́n, Ana Oaknin, Petronella B. Ottevanger, Vilius Rudaitis, Kia Katchar, Zhen Wang, Jane Ruman, Jonathan A. Ledermann

Bibliographic record

VenueJournal of Clinical Oncology · 2018
Typearticle
Languageen
FieldMedicine
TopicOvarian cancer diagnosis and treatment
Canadian institutionsCentre Hospitalier de l’Université de Montréal
Fundersnot available
KeywordsMedicinePembrolizumabCohortOvarian cancerInterimInternal medicineClinical endpointInterim analysisOncologyCancerProgression-free survivalTopotecanChemotherapySurgeryClinical trialImmunotherapy

Abstract

fetched live from OpenAlex

5511 Background: Data from the KEYNOTE-028 study (NCT02054806) suggested that pembrolizumab (pembro) has clinical activity in patients (pts) with PD-L1+ advanced ovarian cancer (AOC). We assessed the antitumor activity and safety of pembro in pts with recurrent AOC in the ongoing, 2-cohort, phase 2 KEYNOTE-100 study (NCT02674061). Methods: Key eligibility criteria included epithelial ovarian, fallopian tube, or primary peritoneal cancer, confirmed recurrence following front-line platinum-based therapy, ECOG PS 0/1, and provision of a tumor sample for biomarker analysis. Cohort A pts received ≤2 prior chemotherapy lines for recurrent AOC and had a platinum-free or treatment-free interval (PFI/TFI) of ≥3 to 12 mo. Cohort B pts received 3-5 prior chemotherapy lines and had a PFI/TFI of ≥3 mo. Pts received pembro 200 mg Q3W IV for 2 yrs or until progression, death, unacceptable toxicity, or consent withdrawal. Tumor imaging was performed every 9 wks for 1 yr and every 12 wks thereafter. Primary study endpoint was ORR per RECIST v1.1 by independent central review for both cohorts and by tumor PD-L1 expression. The effect of PD-L1 expression on ORR was tested with the combined positive score (CPS) assay. Cutpoints were established using the first 100 pts enrolled into Cohort A (training set). Validation was performed among all subsequent pts enrolled. Training set results are presented here. Complete results (n = 378) will be available for presentation. Results: 378 pts were enrolled in KEYNOTE-100. 97/100 training set pts had analyzable results. Mean (±SD) age for this group was 61 (±12) yr, 68% had ECOG PS 0, and 77% had high grade serous disease. ORR was 9% (95% CI, 4, 17). ORR was higher in pts with PD-L1 expression: 14% (8/59) with CPS ≥1 and 25% (5/20) with CPS ≥10. 73% of pts had treatment-related (TR) AEs and 17% had grade 3-5 TR AEs. There was 1 TR death in a pt with Stevens-Johnson syndrome. Conclusions: Pembro monotherapy was associated with antitumor activity in pts with recurrent AOC. ORR increased with PD-L1 expression, better defining a population benefiting from single agent pembro. No new safety signals were identified in this population. Clinical trial information: NCT02674061.

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)0.005
metaresearch head score (Gemma)0.003
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Non-randomized trial · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.005
Threshold uncertainty score0.024

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0050.003
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0010.001
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0010.001
Open science0.0010.001
Research integrity0.0010.002
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 head0.085
GPT teacher head0.470
Teacher spread0.386 · 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 designNon-randomized 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

Citations61
Published2018
Admission routes1
Has abstractyes

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