Treatment-free survival after first-line therapies for metastatic renal cell carcinoma: An International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) analysis.
Bibliographic record
Abstract
390 Background: Patients treated with immune checkpoint blockade (ICB) may experience disease control without need for ongoing systemic therapy, a period not well described by conventional time-to-event endpoints. Treatment-free survival (TFS) represents a novel endpoint to quantify this period. Methods: We identified patients with mRCC from the IMDC dataset initiating first-line systemic therapy with VEGFR monotherapy (sunitinib, pazopanib), combination ICB-VEGFR therapy ([axitinib or envatinib]-pembrolizumab, cabozantinib-nivolumab, axitinib-avelumab), or ICB doublet therapy (ipilimumab-nivolumab) between February 1, 2014, and February 1, 2023. Overall survival from treatment initiation was partitioned into periods including TFS, time on first-line therapy, and survival after subsequent therapy initiation utilizing differences in restricted mean survival time (RMST) over 36-months. TFS was defined as the difference between the 36-month RMST between: (1) time from treatment initiation to discontinuation of first-line therapy, death, or censor at last follow-up and (2) time from treatment initiation to subsequent therapy initiation, death, or censor at last follow-up. Results: 3,758 patients with mRCC initiated first-line VEGFR monotherapy (n=2,635; median age 62 years; 19.1% IMDC favourable risk), ICB-VEGFR regimens (n=354; median age 60 years; 33.3% IMDC favourable risk), or doublet ICB (n=769; median age 62 years; 0% IMDC favourable risk). Patients with favourable IMDC risk initiating VEGFR monotherapy and ICB-VEGFR regimens experienced a TFS duration of 8.5% (3.1 mos 95% CI 1.5 - 4.6) and 10.1% (3.7 mos 95% CI 0.2-7.2) of the 36-month period respectively. Among intermediate/poor risk patients, those treated with VEGFR monotherapy, ICB-VEGFR regimens, and ICB doublet therapy experienced 5.9% (2.1 mos 95% CI 1.4 - 2.8), 10.3% (4.7 mos 95% CI 1.0-6.4), and 14.6% (5.3 mos 95% CI 3.8-6.8) of the 36-month period alive and treatment free respectively. Conclusions: Patients receiving VEGFR monotherapy or ICB-VEGFR combination therapies spent at most 10% of the 36-month period surviving treatment free, while IMDC intermediate/poor risk patients treated with ICB doublet therapy experienced a TFS period of 15% of the 36-month period.[Table: see text]
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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 | 0.005 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.003 | 0.005 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.000 | 0.001 |
| 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".