Incorporation of triapine (T) with cisplatin chemoradiation (CRT) for locally advanced cervical and vaginal cancer: Results from NRG-GY006, a phase III randomized trial.
Bibliographic record
Abstract
5502 Background: Definitive cisplatin-based chemoradiation (CRT) plus brachytherapy for locally advanced cervical cancer (FIGO IB3-IVA) results in sustained survival for 60-70% of patients. Recent studies integrating anti-PD-1 checkpoint immunotherapy (CALLA, NCT03830866) or consolidation chemotherapy (OUTBACK, ACTRN12610000732088) have not demonstrated a survival benefit over CRT. Intrinsic overexpression of ribonucleotide reductase may enhance DNA damage repair due to CRT. We report on the efficacy and tolerability of adding the ribonucleotide reductase inhibitor, triapine, to CRT. Methods: NRG GY006 is a randomized, open-label phase III clinical trial. Eligible patients had FIGO 2009 locally advanced cervical (stages IB2, II, IIIB or IVA without radiographic evidence of para-aortic nodal involvement) or stages II-IV vaginal cancer. Patients were randomly assigned to receive cisplatin (40 mg/m2 weekly) with RT 45 Gy + lymph node boost alone (CRT) or CRT in combination with 15 total infusions of triapine (25 mg/m2 IV) Mon/Wed/Fri (CRT + T). Both image guided IMRT or 3D RT were allowed but needed to be specified and pass a rigorous credentialing process. All RT plans had a pre-treatment review with expert planning feedback to the sites. The primary endpoint was overall survival (OS); secondary endpoint was progression-free survival. Exploratory endpoints included rate of complete metabolic response on post treatment PET/CT imaging at 3 months and knowledge-based planning for image guided IMRT. The target sample was 450 with 127 OS events. The design was to provide 80% power to detect a 10% improvement in OS at 3 years over the control (or HR = 0.6) at 2.5% significance level including one interim futility analysis at 50% information time. Results: Between 1/15/16 and 9/22/22 448 eligible patients were randomized to CRT (n=224) or CRT+T (n=224). The database was locked on 10/18/22 with 69 deaths. Median age was 47 years (range 23-85 years). The majority had cervical cancer (93.3%) and squamous cell carcinoma (82%). 52% had FIGO stage II disease. Racial/ethnic distribution included non-Hispanic white (53.8%), Hispanic/Latina (22.5%), and black (15.2%). IMRT was used in (74.3%) and HDR brachytherapy (98.2%) of cases. No differences in Grade 3-5 toxicities were observed: CRT =52% and CRT +T= 49% with Two G5 toxicities (cardiac arrest and acidosis) in the CRT+T arm. 343 patients have completed all protocol directed therapy. With a median follow-up of 28 months (IQR 15-45 months), the median PFS and OS for both arms were not reached yet. HR for death was 1.018 (95% CI 0.634-1.635), the conditional power was 15% to detect a HR = 0.6 at 100% information time. Conclusions: The addition of triapine to CRT did not improve OS. Clinical trial information: NCT02466971 .
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.002 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.002 | 0.003 |
| Insufficient payload (model declined to judge) | 0.007 | 0.001 |
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".