Record-3: Phase II randomized trial comparing sequential first-line everolimus (EVE) and second-line sunitinib (SUN) versus first-line SUN and second-line EVE in patients with metastatic renal cell carcinoma (mRCC).
Bibliographic record
Abstract
4504 Background: Sequential SUN (tyrosine kinase inhibitor, TKI) until progression of disease (PD) followed by EVE (mTOR inhibitor) is standard therapy for patients with mRCC. This open-label, multicenter, phase II trial compared 1st-line EVE to 1st-line SUN (NCT00903175). Sequential EVE→SUN was also compared with standard SUN→EVE. Methods: Patients with mRCC (clear or non-clear cell) naive to prior systemic therapy were randomized 1:1 to either 1st-line EVE 10 mg/day or SUN 50 mg/day (4 weeks on, 2 weeks off) until PD. Patients then crossed over and continued on the alternate drug until PD. Primary objective was to assess PFS noninferiority of 1st-line EVE to 1st-line SUN; defined as an observed hazard ratio (HR)1st EVE/SUN ≤1.1. Overall survival (OS), combined 1st-line and 2nd-line PFS, and safety were secondary end points. Results: From10/09 to 6/11, 471 patients enrolled (EVE→SUN, n = 238; SUN→EVE, n = 233). Median age was 62 years, 85.4% had clear-cell RCC, and MSKCC favorable/intermediate/poor risk was 30/56/14%. Median follow-up was 22.7 months. A total of 53.7% of patients who discontinued 1st-line EVE entered into 2nd-line SUN and 51.6% of patients who discontinued 1st-line SUN entered into 2nd-line EVE. Median PFS (95% CI) was 7.9 (5.6-8.2) months for 1st-line EVE and 10.7 (8.2-11.5) months for 1st-line SUN. HR1st EVE/1st SUN (95% CI) was 1.43 (1.15-1.77). Median OS (95% CI) was 22.4 (19.7-NA) months for EVE→SUN and 32.0 (20.5-NA) months for SUN→EVE; HREVE-SUN/SUN-EVE (95% CI) was 1.24 (0.94-1.64). A trend in favor of SUN→EVE for OS was observed, but will need to be confirmed with final OS analysis. Additional efficacy results for secondary end points are forthcoming. Common treatment-emergent adverse events for 1st-line EVE vs SUN, respectively, were stomatitis (53% vs 57%), fatigue (45% vs 51%), and diarrhea (38% vs 57%). Conclusions: Noninferiority of PFS for 1st-line EVE compared with SUN was not achieved in this randomized phase II trial of mRCC patients. The treatment paradigm remains SUN→EVE since the sequence achieved optimal clinical benefit. Clinical trial information: NCT00903175.
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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 | 0.002 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.003 | 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 | 0.003 |
| 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".