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First-line therapy for metastatic renal cell carcinoma with pancreatic metastases: Results from the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC).

2022· article· en· W4213180043 on OpenAlexaff
Eduard Roussel, Lisa Kinget, Benoit Beuselinck, Maarten Albersen, Connor Wells, Matthew Scott Ernst, Frede Donskov, Andrew Schmidt, Bernadett Szabados, Sumanta K. Pal, Luís Meza, Neeraj Agarwal, Andrew Weickhardt, Ian D. Davis, Ajjai Alva, Lori Wood, Camillo Porta, Toni K. Choueiri, Daniel Yick Chin Heng, Vishal Navani

Bibliographic record

VenueJournal of Clinical Oncology · 2022
Typearticle
Languageen
FieldMedicine
TopicRenal cell carcinoma treatment
Canadian institutionsDalhousie UniversityUniversity of CalgaryQueen Elizabeth II Health Sciences CentreBC Cancer Agency
Fundersnot available
KeywordsMedicineRenal cell carcinomaNivolumabInternal medicineProportional hazards modelGastroenterologyCarcinomaPopulationUrologyOncologyVascular endothelial growth factorClear cell renal cell carcinomaCancerVEGF receptorsImmunotherapy

Abstract

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317 Background: Metastatic renal cell carcinoma (mRCC) with pancreatic metastases (PM) is characterised by heightened angiogenesis, which is associated with improved outcomes with vascular endothelial growth factor (VEGF) inhibitors. We aimed to compare the efficacy of first-line (1L) ipilimumab/nivolumab (IOIO) vs. anti-PD(L)1/anti-VEGF (IOVE) vs. VEGF monotherapy (VE) in mRCC patients with and without PM. Methods: We performed a retrospective analysis of patients with and without PM, using the IMDC. Sites of metastases were captured at initiation of 1L. Patients with PM could also have metastases at other sites. We studied overall survival (OS) from start of 1L therapy using Cox regression, adjusted for IMDC risk groups. Kaplan Meier survival curves were generated. Results: 543/7,634 (7%) patients had PM. Patients with PM in the overall population had improved OS compared to those without, 56 vs 25.6 months respectively (HR 0.63, 95% CI 0.55-0.73, p<0.0001). When examining the effect of PM within 1L options, those treated with IOVE exhibited a longer OS if PM were present vs absent, median not reached vs 45 months respectively (HR 0.41, 95% CI 0.18-0.93 p=0.03). This association was also seen in patients with treated with 1L VE, in those with PM vs absent, median 53.1 vs 25.1 months respectively (HR 0.65, 95% CI 0.55-0.76, p <0.0001). Contrastingly there was no difference in median OS of patients with or without PM in patients receiving IOIO, 41.4 vs 44.4 months respectively (HR 0.86, 95% CI 0.48-1.56, p=0.62). Comparing the outcomes between 1L therapies in patients with PM the median OS of IOVE vs VE was not reached vs 53.1 months respectively (HR 0.37, 95% CI 0.16-0.83 p=0.02). Conversely, upfront VE and IOIO had a similar median OS of 53.1 vs 41.4 months respectively (HR 0.81, 95% CI 0.45-1.47 p=0.49). We were unable to find any difference in OS between those treated with IOVE vs IOIO, median not reached vs 41.4 months respectively (HR 0.52 95%, CI 0.19-1.45, p=0.21), but the low event rate limited this interpretation. Conclusions: We found that the presence of PM leads to an indolent biological behavior and was associated with improved outcomes when 1L therapy included a VE component. PM patients had comparable OS outcomes on 1L VE and 1L IOIO therapy, but improved OS when treated with 1L IOVE. Anti-angiogenic therapy may be necessary to optimize outcomes in PM and this warrants prospective evaluation. [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)0.006
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 score0.013
Threshold uncertainty score0.026

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0030.006
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.001
Bibliometrics0.0020.006
Science and technology studies0.0000.000
Scholarly communication0.0020.001
Open science0.0010.001
Research integrity0.0000.001
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 head0.137
GPT teacher head0.391
Teacher spread0.254 · 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".

Quick stats

Citations3
Published2022
Admission routes1
Has abstractyes

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