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
Bibliographic record
Abstract
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.
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 imitationNot 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.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
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.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
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".