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PSMAddition: A phase 3 trial to compare treatment with <sup>177</sup>Lu-PSMA-617 plus standard of care (SoC) and SoC alone in patients with metastatic hormone-sensitive prostate cancer.

2023· article· en· W4379282239 on OpenAlexaff
Scott T. Tagawa, Oliver Sartor, Fred Saad, Alison Helen Reid, Olga V. Sakharova, Felix Y. Feng, Karim Fizazi, Michael J. Morris

Bibliographic record

VenueJournal of Clinical Oncology · 2023
Typearticle
Languageen
FieldMedicine
TopicProstate Cancer Treatment and Research
Canadian institutionsUniversité de Montréal
Fundersnot available
KeywordsMedicineProstate cancerAndrogen deprivation therapyClinical endpointOncologyInternal medicineEnzalutamideUrologyCancerRandomized controlled trialAndrogen receptor

Abstract

fetched live from OpenAlex

TPS5116 Background: Lutetium ( 177 Lu) vipivotide tetraxetan ( 177 Lu-PSMA-617) plus protocol-permitted standard of care (SoC) significantly improved radiographic progression-free survival (rPFS) and overall survival (OS) in patients with prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer, previously treated with at least one androgen receptor pathway inhibitor (ARPI) and one or two taxanes. Androgen deprivation therapy (ADT) and ARPIs may alter PSMA expression and radiosensitivity. PSMAddition will assess the efficacy and safety of 177 Lu-PSMA-617 plus SoC versus SoC alone in adults with metastatic hormone-sensitive prostate cancer (mHSPC). Methods: PSMAddition (NCT04720157) is an international, prospective, open-label, randomized, phase 3 trial, with crossover, in adults with mHSPC. Eligible patients are treatment-naive or minimally treated candidates for hormonal therapy, with PSMA-positive disease (determined by 68 Ga-PSMA-11 PET/CT), ECOG performance status of 0 to 2 and adequate major organ function. Patients are excluded if they have rapidly progressing tumors that require chemotherapy. Approximately 1126 patients will be randomized 1:1 to receive 177 Lu-PSMA-617 (7.4 GBq every 6 weeks for a maximum of 6 cycles) plus SoC or SoC alone (an ARPI and ADT). Stratification factors are tumor volume (high/low), age (≥ 70/ &lt; 70 years), and previous/planned prostatectomy or radiation treatment of the primary prostate tumor (yes/no). Recruitment for a China extension cohort (40–60 patients) will follow after completion of main study recruitment. The primary endpoint is rPFS, as assessed by blinded independent centralized review. Upon centrally confirmed radiographic progression, participants in the SoC-only arm can cross over to the 177 Lu-PSMA-617 arm. The planned sample size provides 95% power to detect a hazard ratio of 0.7 for rPFS after 418 events with an overall one-sided significance level of 0.025. The key secondary endpoint is OS, others include the proportion of patients with a prostate-specific antigen (PSA) decline of ≥ 90% from baseline, time to development of metastatic castration-resistant prostate cancer, composite PFS (radiographic, clinical or PSA progression), safety and tolerability, and health-related quality of life. Imaging and biospecimen (tissue and blood) collection is embedded for correlative analysis. Participants who have received 177 Lu-PSMA-617 will have the option to enroll in a separate long-term safety follow-up study. Updated from previous presentation at the 2021 European Society for Medical Oncology Congress, FPN 3035, with permission. Clinical trial information: NCT04720157 .

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 distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation 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 score0.334
Threshold uncertainty score0.610

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0020.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

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 head0.112
GPT teacher head0.479
Teacher spread0.367 · 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 teacher head, 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

Citations30
Published2023
Admission routes1
Has abstractyes

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