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Final safety results from ATHENA–MONO (GOG-3020/ENGOT-ov45), a randomized, placebo-controlled, double-blind, phase 3 trial evaluating rucaparib monotherapy as maintenance treatment in patients with newly diagnosed ovarian cancer.

2024· article· en· W4399380599 on OpenAlexaff
David M. O’Malley, Bradley Monk, Myong Cheol Lim, José Fuentes Pradera, Joseph Buscema, Michelle Wilson, Rocco De Vivo, Thomas J. Herzog, Flora Zagouri, Amit M. Oza, Olga N. Mikheeva, John P. Diaz, Alla Lisyanskaya, Robert Morris, Ilan Bruchim, Marcia Craib, Christy Connor, Danny Shih, Keiichi Fujiwara, Rebecca Kristeleit

Bibliographic record

VenueJournal of Clinical Oncology · 2024
Typearticle
Languageen
FieldMedicine
TopicPARP inhibition in cancer therapy
Canadian institutionsPrincess Margaret Cancer Centre
Fundersnot available
KeywordsMedicinePlaceboOvarian cancerDouble blindRandomized controlled trialOncologyInternal medicineSurgeryCancerAlternative medicine

Abstract

fetched live from OpenAlex

5554 Background: Rucaparib provided a sustained progression-free survival benefit in patients (pts) with newly diagnosed advanced ovarian cancer after first-line treatment in the phase 3 ATHENA-MONO study (NCT03522246). We report final safety analyses (data cutoff 09 Mar 2023). Methods: Rucaparib was administered in 28-day cycles. Eligible pts were randomized 4:1 to oral rucaparib 600 mg BID (N=427) or placebo (N=111), with a treatment cap defined as 24 months. The safety population included randomized pts who received at least 1 dose of study drug (rucaparib, n=425; placebo, n=110). Results: All ATHENA-MONO pts discontinued treatment as of 24 Nov 2022 with a median treatment duration of 15 months and 35% of pts reaching the 24-month treatment cap. The median (range) relative dose intensity was 89% (30-110) for rucaparib. The rate of treatment-emergent adverse events (TEAEs), grade ≥3 TEAEs, TEAEs leading to interruption, dose reduction, or discontinuation with rucaparib remained consistent with the primary endpoint analysis with some minor changes (see Table below). Most common grade ≥3 TEAEs were anemia/decreased hemoglobin (28.7%), neutropenia/decreased neutrophils (14.6%), increased ALT/AST (10.6%), and thrombocytopenia/decreased platelets (7.3%). The most common TEAEs leading to discontinuation were anemia/decreased hemoglobin (3.5%), asthenia/fatigue (4.9%), and nausea (2.1%). Hypertension continued to be the most common TEAE observed in the placebo group (3.6%) compared with 1.6% in the rucaparib group. There were no changes in the incidence of serious adverse events or TEAEs leading to death since the primary endpoint analysis. Myelodysplastic syndromes (MDS)/acute myeloid leukemia (AML) were reported in a total of 3 pts in the rucaparib group (1 MDS during treatment [0.2%] and 1 AML and 1 MDS during long-term follow-up [0.5%]), of which the latter occurred since the primary readout. The initial MDS event that occurred during treatment, included in these incidence numbers, was considered resolved by the investigator since the initial analysis. Conclusions: Long-term maintenance treatment with rucaparib demonstrates a consistent and manageable safety profile in a broad population of pts with newly diagnosed ovarian cancer. No new safety signals were identified. Adverse events were generally manageable and led to discontinuation in a low proportion of pts. Clinical trial information: NCT03522246 . [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)0.004
metaresearch head score (Gemma)0.004
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 score0.013
Threshold uncertainty score0.042

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0040.004
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 science0.0010.000
Research integrity0.0020.002
Insufficient payload (model declined to judge)0.0130.002

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 head0.166
GPT teacher head0.501
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 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

Citations5
Published2024
Admission routes1
Has abstractyes

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