Abstract 2429: Longitudinal ctDNA monitoring using a high sensitivity tumor-informed assay in patients with metastatic HR+/HER2− breast cancer receiving endocrine therapy and CDK4/6 inhibitors
Notice bibliographique
Résumé
Abstract BACKGROUND: ctDNA burden is prognostic and its dynamics during therapy may permit innovative strategies in metastatic breast cancer (mBC). Previous analyses have focused on driver genes, with limited sensitivity to quantify depth of response or detect early molecular progression. To enable sensitive, quantitative ctDNA monitoring, we analyzed samples from a cohort of HR+/HER2− mBC pts treated with endocrine therapy (ET) and CDK4/6 inhibitors (CDKi) using RaDaR, a patient-specific assay that tracks tumor-informed truncal variants independent of driver status with a limit of detection of 0.001%. METHODS: HR+/HER2− mBC pts receiving standard ET + CDKi were enrolled in a prospective observational cohort from 2018. Plasma samples were collected at baseline (BL), within 30 days (d), and ~q3 months (mo) with radiological scans. RaDaR was performed on all samples for pts with tissue available for WES (as per assay). Clinico-pathological variables were collected. Endpoints were time to treatment failure (TTF) and overall survival (OS). RESULTS: 51 pts were available for analysis. Median age was 60 years (range 38-88), 63% had visceral disease, and most pts were treated as first (75%) or second (20%) line. RaDaR was successful on 43 pts, with the rest dropping out due to failed WES (1) or panel failure (7). Archival tissue WES was used to design bespoke assays targeting a median 48 (23-52) variants in 248 samples, with a median of 5 samples/pt (2-14) collected over a median follow up of 27.8 (0.9-64.3) mo. ctDNA was detected in 91% (39/43) of BL and 70% (174/248) of all samples, with a median estimated variant allele fraction (eVAF) of 0.05%. Higher BL eVAFs were associated with liver disease (p=0.02) and with shorter TTF (p<0.01 adjusted by age and visceral disease) and OS (p<0.01). 36/39 pts had ≥1 sample with ctDNA decrease from BL, occurring within the first mo of therapy in 77% (24/31) of pts with available early samples. In 13 pts ctDNA became undetectable (‘suppressed’) at a median time (T) of 157 d (14-343). Among 25 pts with treatment failure (TF), the median T from the last negative/decreasing eVAF to TF was 163 d (0-943). Only 3 pts with TF had prior negative ctDNA, occurring with a median lead T of 198 d (119-595). Among ongoing pts, the median T from the last ctDNA decrease to last follow up was 317 d (163-1508), and from the last negative ctDNA sample was 352 d (163-993). CONCLUSION: RaDaR enabled sensitive ctDNA monitoring in 91% HR+/HER2− mBC pts on ET + CDK4/6i. ctDNA levels were prognostic and fell rapidly with therapy, but suppression occurred in less than one-third of pts, taking a median of 5.2 mo. Pts with negative/decreasing ctDNA may require less frequent clinical/radiographic tumor evaluations. Highly sensitive ctDNA tracking may inform prognostic assessments, follow up strategies, and innovative interventional trial designs. Citation Format: Jesus Fuentes-Antras, Mitchell J. Elliott, Philippe Echelard, Aaron Dou, Zachary Veitch, Philippe L. Bedard, Eitan Amir, Michelle B. Nadler, Nicholas Meti, Nancy Gregorio, Elizabeth Shah, Emily Van de Laar, Celeste Yu, Lisa Gates, Clodagh Murray, Christopher G. Smith, Amber Chevalier, Lillian L. Siu, Hal K. Berman, David W. Cescon. Longitudinal ctDNA monitoring using a high sensitivity tumor-informed assay in patients with metastatic HR+/HER2− breast cancer receiving endocrine therapy and CDK4/6 inhibitors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2429.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,001 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,001 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».