Final clinical results of a randomized phase II international trial of everolimus vs. sunitinib in patients with metastatic non-clear cell renal cell carcinoma (ASPEN).
Bibliographic record
Abstract
4507 Background: Limited evidence exists to guide therapeutic decisions in patients (pts) with metastatic non-clear cell RCC (NC-RCC). Methods: ASPEN was an international, randomized trial of pts with metastatic papillary, chromophobe, or unclassified histology; any MSKCC risk group, and no prior systemic therapy. Pts were randomized 1:1 to either everolimus (E) or sunitinib (S) until progression, stratified by histology and risk group. The primary endpoint was radiographic PFS by RECIST 1.1. With an expected 90 PFS events, there was 83% power to detect a 38% decrease in the hazard rate of progression/death assuming a two-sided type I error of 0.20 using a stratified log-rank statistic. Results: Between September 2010 and October 2013,we enrolled108 subjects across 17 sites and 3 countries. Median age was 63, 75/25% male/female, 66% papillary, 15% chromophobe, 19% unclassified; 27/59/14% good/intermediate/poor risk; 57 vs. 51 were randomized to E vs S. Treatment arms were well balanced at baseline. With 87 PFS events, 53 deaths, and 2 pts remaining on study treatment, S improved overall PFS, meeting the primary endpoint. S improved PFS in good/intermediate risk and papillary/unclassified pts, but E improved PFS in poor risk and chromophobe pts (Table). No unexpected safety signals emerged. Conclusions: Sunitinib prolonged rPFS as compared with everolimus in patients with NC-RCC, but resulted in higher rates of severe toxicity. This is the largest trial to date in NC-RCC and the first to demonstrate an mTOR-sensitive subgroup of NC-RCC pts as compared with VEGF inhibition in the front-line setting, including chromophobe and poor risk RCC pts. Clinical trial information: NCT01108445. Endpoint E (n=57) S (N=51) HR (80% CI) S as Reference p-value Median PFS (mo) (80% CI) Papillary Chromophobe Unclassified Risk: Good Intermediate Poor 5.6 5.5-6.0 5.5 11.4 5.6 5.7 4.9 6.1 8.3 5.8-11.1 8.1 5.5 11.5 14.0 6.5 4.0 1.41 (1.03-1.92) 1.52 (1.05-2.20) 0.71 (0.31-1.65) 2.55 (1.01-6.45) 3.07 (1.51-6.28) 1.38 (0.96-2.00) 0.21 (0.06-0.69) 0.16 Median OS (mo, 95% CI) 13.2 31.5 1.17 (0.65-2.14) 0.60 Objective Response Rate (%) CR+ PR % SD % PD % Missing % 5 12 67 16 4 31 61 4 - - >Grade 3 Treatment-Related AEs (%) 47% 65% - -
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 | 0.004 | 0.003 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.002 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.008 | 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".