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Long-term OS for patients with advanced NSCLC enrolled in the KEYNOTE-001 study of pembrolizumab (pembro).

2016· article· en· W2516660524 on OpenAlexaff
Rina Hui, Leena Gandhi, Enric Carcereny, Enriqueta Felip, Myung‐Ju Ahn, Joseph P. Eder, Ani Sarkis Balmanoukian, Natasha B. Leighl, Charu Aggarwal, Leora Horn, Amita Patnaik, Gary Middleton, Matthew A. Gubens, Matthew D. Hellmann, Jean‐Charles Soria, Suresh S. Ramalingam, Gregory M. Lubiniecki, Jin Zhang, Bilal Piperdi, Edward B. Garon

Bibliographic record

VenueJournal of Clinical Oncology · 2016
Typearticle
Languageen
FieldMedicine
TopicCancer Immunotherapy and Biomarkers
Canadian institutionsPrincess Margaret Cancer CentreUniversity Health Network
Fundersnot available
KeywordsMedicinePembrolizumabDiscontinuationInternal medicineOncologyCancerImmunotherapy

Abstract

fetched live from OpenAlex

9026 Background: The anti–PD-1 antibody pembro (MK-3475) is approved in the US for treating PD-L1–positive NSCLC that progressed after platinum-containing chemotherapy. This approval was based on data from the large, phase 1b KEYNOTE-001 study (NCT01295827). We present updated, long-term OS data for treatment-naive and previously treated patients (pts) enrolled in KEYNOTE-001. Methods: 550 pts received pembro 2 or 10 mg/kg Q3W or 10 mg/kg Q2W until intolerable toxicity, progression, or investigator decision. PD-L1 was assessed by IHC using the 22C3 antibody, with positivity defined as PD-L1 expression on ≥1% of tumor cells (tumor proportion score [TPS] ≥1%). Response was assessed by RECIST v1.1 every 9 wk. Survival was assessed every 2 mo after discontinuation. Results: As of Sep 18, 2015, median follow-up duration was 23.1 mo. Median OS (95% CI) was 22.1 mo (17.1-27.2) for treatment-naive pts and 10.6 mo (8.6-13.3) for previously treated pts. 18-mo OS rates were 58.2% and 37.0% respectively; 24-mo rates were 44.5% and 31.3%. OS increased with increasing PD-L1 TPS (Table). OS by smoking history, histology, and EGFR status is shown (Table). Conclusions: Pembrolizumab provides long-term OS benefit for PD-L1–positive treatment-naive and previously treated NSCLC. Along with data from KEYNOTE-010, these data support both PD-L1 as a predictive biomarker for pembro and the benefit of pembro in pts with PD-L1–positive (TPS ≥1%) NSCLC. The 22.1-mo median OS in treatment-naive pts with PD-L1–positive tumors is very promising and compares favorably with that of standard-of-care chemotherapy. Clinical trial information: NCT01295827.Median OS (95% CI), mo Treatment Naive N = 101 Previously Treated N = 449 PD-L1 TPS ≥1% n = 79 22.1 (16.7-27.2) n = 306 11.3 (8.3-14.0) ≥50% n = 27 NR (22.1-NR) n = 138 15.4 (10.6-18.5) 1%-49% n = 52 19.5 (10.7-22.2) n = 168 8.2 (6.0-12.7) PD-L1 TPS <1% n = 12 14.7 (3.4-NR) n = 90 8.6 (5.5-12.0) Squamous n = 19 15.6 (6.0-21.0) n = 76 14.7 (10.4-18.4) Nonsquamous n = 79 26.3 (22.0-NR) n = 367 9.4 (7.3-12.6) Current/former smoker n = 90 22.0 (16.7-27.2) n = 324 12.2 (9.2-14.3) Never smoker n = 11 NR (16.2-NR) n = 125 7.6 (5.9-12.1) EGFR wild type * n = 335 12.1 (9.1-14.3) EGFR mutant * n = 74 6.0 (4.6-9.9) *Pts with EGFR-mutant, treatment-naive NSCLC were ineligible.

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)0.001
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.002
Threshold uncertainty score0.008

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0020.001
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 science0.0000.000
Research integrity0.0010.002
Insufficient payload (model declined to judge)0.0020.001

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 head0.062
GPT teacher head0.439
Teacher spread0.377 · 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 designObservational
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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Citations61
Published2016
Admission routes1
Has abstractyes

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