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Patient-reported outcomes (PRO) in patients (pts) with <i>BRCA1/2</i>-altered metastatic castration-resistant prostate cancer (mCRPC) receiving niraparib (NIRA) with abiraterone acetate and prednisone (AAP): Results from MAGNITUDE study.

2024· article· en· W4391302045 on OpenAlexaff
Dana E. Rathkopf, Guilhem Roubaud, Kim N., Eleni Efstathiou, Gerhardt Attard, David Olmos, Eric J. Small, Marniza Saad, Elena Castro, Won Kim, Daphne Wu, Kristi Bertzos, Shiva Dibaj, Jenny Zhang, Peter Francis, Matthew R. Smith

Bibliographic record

VenueJournal of Clinical Oncology · 2024
Typearticle
Languageen
FieldMedicine
TopicPARP inhibition in cancer therapy
Canadian institutionsUniversity of British Columbia
Fundersnot available
KeywordsMedicineAbiraterone acetateProstate cancerPrednisoneAbirateroneInternal medicineOncologyCancerCastrationAndrogen deprivation therapyHormoneAndrogen receptor

Abstract

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105 Background: MAGNITUDE, an international phase 3 randomized double-blind study, demonstrated that mCRPC pts with BRCA1/2 alterations receiving NIRA + AAP had significantly improved radiographic progression-free survival, and clinically relevant prolongations in time to symptomatic progression and time to cytotoxic chemotherapy compared with placebo (PBO) + AAP. Here, we report PRO results (pain, health-related quality of life [HRQoL], and side effect bother) in the BRCA1/2 subset of mCRPC pts in the final analysis of MAGNITUDE. Methods: Pts were screened prospectively for homologous recombination repair (HRR) gene alterations. Eligible pts had ECOG status ≤1 and a Brief Pain Inventory–Short Form (BPI-SF) worst pain score ≤3 (scale of 0-10), and were randomized 1:1 to NIRA + AAP or PBO + AAP orally daily in 28-day cycles. PRO assessments on day 1 of specified cycles included BPI-SF and Functional Assessment of Cancer Therapy–Prostate (FACT-P). Time to deterioration (TTD) in pain (BPI-SF worst, average, and pain interference, and FACT-P pain-related scale [PRS]) were compared between treatment arms using proportional hazards regression models. Changes from baseline in HRQoL (FACT-P total, scale of 0-156) were compared using repeated measures analysis, and side-effect bother was assessed in both arms as a single item from FACT-P (GP5). Results: PRO compliance for FACT-P and BPI-SF was >85% in 225 pts with BRCA1/2-altered mCRPC. At baseline, mean BPI-SF pain scores was 1.09 (SD, 1.57) in NIRA + AAP and 1.35 (SD, 1.98) in PBO + AAP. Mean FACT-P Total in NIRA + AAP and PBO + AAP was 116.33 (SD, 18.42) and 114.8 (SD, 18.9), respectively. Median TTD in BPI-SF worst pain, pain interference, average pain, and FACT-P PRS were numerically longer for NIRA + AAP vs. PBO + AAP (Table). Repeated measures results showed HRQoL was maintained on treatment for the BRCA subgroup with no clinically meaningful differences in the FACT-P total score over time or between treatment arms. Analysis of FACT-P item GP5 in the BRCA subset showed side effect bother was rated “not at all” or “a little bit” by 87% of NIRA + AAP and 92% of PBO + AAP subjects across treatment cycles. Conclusions: In pts with BRCA1/2-altered mCRPC, NIRA + AAP maintained HRQoL. Pts experienced minimal bother from side effects associated with treatment. These data further support the benefit-risk profile of NIRA + AAP for the treatment of mCRPC pts with BRCA1/2 alterations. Clinical trial information: NCT03748641 . [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)0.001
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: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.001
Threshold uncertainty score0.007

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.001
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0010.000

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 head0.097
GPT teacher head0.432
Teacher spread0.335 · 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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Citations2
Published2024
Admission routes1
Has abstractyes

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