Efficacy and safety of everolimus in advanced, progressive, nonfunctional neuroendocrine tumors (NET) of the gastrointestinal (GI) tract and unknown primary: A subgroup analysis of the phase III RADIANT-4 trial.
Bibliographic record
Abstract
315 Background: In the groundbreaking, phase 3 RCT RADIANT-4 study, everolimus (EVE) significantly prolonged median progression-free survival (PFS) by 7.1 mo in patients (pts) with advanced, progressive, nonfunctional NET of GI or lung vs placebo (PBO); HR, 0.48 (95%CI, 0.35-0.67), P<0.00001 [Yao JC et al, ECC-ESMO, 2015]. Methods: InRADIANT-4, pts with advanced, progressive, well-differentiated (G1/G2), nonfunctional GI or lung NET were randomized (2:1) to EVE (10 mg/d) or PBO. In this analysis, pts with NET of GI tract (stomach, colon, rectum, appendix, caecum, ileum, duodenum, jejunum, or small intestine) and unknown primary were included. Results: Of 302 pts, 175 had GI NET (EVE [n=118], PBO [n=57]); 36 had NET of unknown primary (EVE [23], PBO [13]). In GI NET pts, median age was 63 y; females: 55%; G1/G2: 75%/25%; WHO PS: 0, 78% or 1, 22%; Caucasian: 73%. Similar baseline characteristics were observed in pts with NET of unknown primary. Ileum (41%), rectum (23%) and jejunum (13%) were the most common locations in GI subgroup. The table below lists prior treatments. In pts with GI NET, median PFS (95% CI) by central review (EVE vs PBO) was 13.1 (9.2-17.3) mo vs 5.4 (3.6-9.3) mo with an estimated 44% risk-reduction in favor of EVE (HR, 0.56; 95% CI, 0.37-0.84). In pts with NET of unknown primary, median PFS (95% CI) by central review (EVE vs PBO) was 13.6 (4.1-not evaluable) mo vs 7.5 (1.9-18.5) mo (HR, 0.60; 95% CI, 0.24-1.51). The most frequent G3/4 adverse events irrespective of drug-relationship reported in ≥5% pts in GI subgroup were diarrhea, hypertension, stomatitis, abdominal pain, fatigue, and acute renal failure. Conclusions: The present subgroup analysis of RADIANT-4 study demonstrated improvement in PFS with EVE for pts with GI NET, and suggests efficacy in NET of unknown primary, with an estimated 40% to 44% risk-reduction in favor of EVE vs PBO. Safety profile for EVE is consistent with that previously reported. Clinical trial information: NCT01524783. [Table: see text]
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.012 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".