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Avelumab first-line (1L) maintenance for advanced urothelial carcinoma (UC): Analysis of clinical and genomic subgroups from the JAVELIN Bladder 100 trial.

2021· article· en· W3168444608 on OpenAlexaff
Thomas Powles, Daniel P. Petrylak, Se Hoon Park, Srikala S. Sridhar, Claudia Caserta, Antoine Thiery Vuillemin, Hyo Jin Lee, Joaquim Bellmunt, Yoshiaki Yamamoto, Jeanny B. Aragon‐Ching, Bo Huang, Keith A. Ching, Craig B. Davis, Alessandra di Pietro, Yohann Loriot, Petros Grivas

Bibliographic record

VenueJournal of Clinical Oncology · 2021
Typearticle
Languageen
FieldMedicine
TopicBladder and Urothelial Cancer Treatments
Canadian institutionsPrincess Margaret Cancer CentreUniversity Health Network
Fundersnot available
KeywordsMedicineAvelumabMetastatic Urothelial CarcinomaCarboplatinGemcitabineInternal medicineOncologyBladder cancerClinical endpointCystectomyChemotherapyCisplatinClinical trialPembrolizumabCancerUrothelial carcinomaImmunotherapy

Abstract

fetched live from OpenAlex

4520 Background: In the phase 3 JAVELIN Bladder 100 trial, avelumab 1L maintenance + best supportive care (BSC) significantly prolonged overall survival (OS) vs BSC alone in patients (pts) with advanced UC that had not progressed on 1L platinum-based chemotherapy (HR, 0.69 [95% CI: 0.56, 0.86; 1-sided P= 0.0005]). We report post hoc analyses in previously unreported clinical and genomic subgroups. Methods: In JAVELIN Bladder 100 (NCT02603432), eligible pts had unresectable locally advanced or metastatic UC without progression after 4-6 cycles of 1L gemcitabine + cisplatin or carboplatin, and were randomized to receive avelumab + BSC (n = 350) or BSC alone (n = 350). The primary endpoint was OS, in all randomized pts and pts with PD-L1+ tumors (Ventana SP263 assay). In this exploratory analysis, we analyzed OS in disease stage and site subgroups, in pts with PD-L1+ tumors who received 1L gemcitabine + carboplatin, and in genomic subtypes (RNAseq whole-transcriptome profiling of tumor tissue) defined using data from The Cancer Genome Atlas (TCGA 2017). Interaction tests were not performed. Results: Prolonged OS was observed in the avelumab + BSC arm vs the BSC alone arm in pts with upper or lower tract tumors, metastatic or locally advanced (LA) and unresectable disease (prior to chemotherapy), and lymph node-only disease post-chemotherapy (Table). OS was also prolonged with avelumab + BSC in pts in PD-L1+ tumors who had received 1L gemcitabine + carboplatin, consistent with findings in the overall population. In genomic subtypes, the OS benefit for avelumab + BSC was apparent across TCGA subtypes except luminal. Conclusions: An OS benefit was seen for avelumab 1L maintenance + BSC vs BSC alone across subgroups of interest. Results are consistent with previously reported findings, further supporting avelumab 1L maintenance as a standard of care for pts with advanced UC that has not progressed with 1L platinum-containing chemotherapy. Clinical trial information: NCT02603432. [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)0.003
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 score0.003
Threshold uncertainty score0.018

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0030.002
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0010.002
Bibliometrics0.0000.000
Science and technology studies0.0000.001
Scholarly communication0.0010.001
Open science0.0010.001
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0020.000

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 head0.132
GPT teacher head0.452
Teacher spread0.320 · 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

Citations14
Published2021
Admission routes1
Has abstractyes

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