Abstract S3-01: The TNT trial: A randomized phase III trial of carboplatin (C) compared with docetaxel (D) for patients with metastatic or recurrent locally advanced triple negative or <i>BRCA1/2</i> breast cancer (CRUK/07/012)
Bibliographic record
Abstract
Abstract Introduction: Subgroups within sporadic triple negative breast cancers (TNBCs) appear to share impaired DNA damage response mechanisms with BRCA1/2 mutation-associated breast cancers. This has been hypothesised to confer particular sensitivity to DNA-damaging platinum chemotherapy. The TNT trial, a randomized phase III trial in women with metastatic or recurrent locally advanced TNBC or BRCA1/2 mutation-associated breast cancer, aimed to test this hypothesis and examine treatment effect in biological subgroups. Patients & Methods: Eligible patients had either ER-, PR-, HER2- breast cancer or were known BRCA1/2 carriers (any ER/PR/HER2). Patients were randomized (1:1) to receive either C (AUC 6 q3wk) or D (100mg/m2 q3wk) for 6-8 cycles or until disease progression if sooner and could cross over to the alternative treatment on confirmed progression. Ineligible patients included those who had ECOG performance status >2, received adjuvant taxane therapy in the last 12 mths, any previous treatment with a platinum chemotherapy, or previous non-anthracycline chemotherapy for metastatic disease. For consenting patients a blood sample and archived tissue samples were obtained for BRCA1/2 genotyping and central biomarker analysis (primary tumour, lymph nodes and recurrent tumour biopsy if available) of subtypes within TNBC and biomarkers of DNA repair deficiency. The primary endpoint was RECIST objective tumour response up to cycle 6 of randomised treatment. Secondary endpoints included toxicity, progression free survival (PFS), time to progression and overall survival. TNT aimed to detect a 15% improvement in ORR with C compared to D, with planned target sample size range of 370-450 depending on assumed ORR in D patients (2-sided α=0.05, power=90%). 376 (188 C, 188 D) were recruited from 74 UK centres between Apr 08 and Mar 14. Results: A snapshot of the data was taken on 30/5/14 at which point 336 (89.4%) patients had experienced a PFS event, with overall median PFS time of 4.4 mths. Median age of patients was 55 yrs (IQR 48-63). 366/376 (97%) patients had TNBC of whom 18 were also known BRCA1/2 mutation carriers, with the remaining 10 patients receptor +ve and BRCA1/2 carriers. 338/376 (90%) had metastatic and 38/376 (10%) recurrent locally advanced disease. 53% had liver or lung metastases affecting the parenchyma and 34% had received previous adjuvant taxane therapy. Median time from initial diagnosis to entering TNT was 2.2 yrs (IQR 1.5-3.5). Primary tumour tissue has currently been received for 277 patients, blood from 286 patients and recurrent tumour tissue from 85 patients. Discussion: TNT will report evidence on the activity of single agent platinum chemotherapy compared with single agent taxane in patients with TNBC and BRCA1/2 associated breast cancer. Correlative analyses of BRCA1/2 mutation status, subtypes and DNA repair biomarkers will also be reported. TNT will be the first randomised trial to report the activity of platinum compared with standard chemotherapy within TNBC subtypes and in relation to BRCA1/2 mutation status and DNA repair biomarkers. Safety, tolerability and response to crossover treatment will also be presented. Citation Format: Andrew Tutt, Paul Ellis, Lucy Kilburn, Cheryl Gilett, Sarah Pinder, Jacinta Abraham, Sophie Barrett, Peter Barrett-Lee, Stephen Chan, Maggie Cheang, Mitch Dowsett, Lisa Fox, Patrycja Gazinska, Anita Grigoriadis, Alexander Gutin, Catherine Harper-Wynne, Matthew Hatton, Sarah Kernaghan, Jerry Lanchbury, James Morden, Julie Owen, Jyoti Parikh, Peter Parker, Nazneen Rahman, Rebecca Roylance, Adam Shaw, Ian Smith, Rose Thompson, Kirsten Timms, Holly Tovey, Andrew Wardley, Gregory Wilson, Mark Harries, Judith Bliss. The TNT trial: A randomized phase III trial of carboplatin (C) compared with docetaxel (D) for patients with metastatic or recurrent locally advanced triple negative or BRCA1/2 breast cancer (CRUK/07/012) [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr S3-01.
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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 | 0.002 | 0.001 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.002 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.002 | 0.004 |
| Insufficient payload (model declined to judge) | 0.013 | 0.002 |
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.
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".