Nintedanib (N) plus best supportive care (BSC) versus placebo (P) plus BSC for the treatment of patients (pts) with colorectal cancer (CRC) refractory to standard therapies: Subanalysis of the phase III LUME-colon 1 study in pts by prior regorafenib (R) treatment.
Bibliographic record
Abstract
660 Background: N is a triple angiokinase inhibitor (including VEGFR, PDGFR and FGFR). LUME-Colon 1 (NCT02149108) evaluated the efficacy and safety of N in pts with metastatic CRC (mCRC) after failure of standard therapies and showed a statistically significant improvement in progression-free survival (PFS) (HR [95% CI]: 0.58 [0.49–0.69]; p < 0.0001) but no difference in overall survival (OS) (HR: 1.01 [0.86–1.19]; p = 0.8659). Here, we report results of a prespecified subanalysis in pts by prior R treatment. Methods: Eligible pts (aged ≥ 18 years; ECOG PS 0–1; mCRC adenocarcinoma refractory to standard treatments, including oxaliplatin, irinotecan, fluoropyrimidines, anti-VEGF and anti-EGFR in RAS wt) were randomised 1:1 to N (200 mg bid) + BSC or P (bid) + BSC. Prior R treatment was a stratification factor. Co-primary endpoints were PFS by central review and OS. Results: 768 mCRC pts were randomised; 285 (37%) had received prior R (N, n = 141; P, n = 144) and 483 (63%) were R naïve (N, n = 245; P, n = 238). Baseline characteristics were similar between the groups (pretreated vs naïve) except: race (Asian: 39% vs 19%), time from first diagnosis ( ≥ 36 months [m]: 67% vs 48%), time from onset of metastatic disease ( ≥ 24 m: 85% vs 64%). Median PFS (N vs P) was 1.5 vs 1.4 m (HR: 0.61 [0.47–0.79]) in prior R pts and 1.5 vs 1.4 m (HR: 0.62 [0.51–0.76]) in R-naïve pts (interaction p-value = 0.9245). Median OS (N vs P) was 6.5 vs 4.6 m (HR: 0.90 [0.69–1.17]) in prior R pts and 6.3 vs 6.6 m (HR: 1.09 [0.89–1.33]) in R-naïve pts (interaction p-value = 0.2529). N was tolerable in both subgroups; AEs leading to discontinuation (N vs P) occurred in 12% vs 8% of prior R pts and 16% vs 12% of R-naïve pts. The most frequent AEs with N were diarrhoea, nausea and vomiting in both subgroups. Conclusions: N demonstrated clinical activity in CRC regardless of prior R treatment; significant improvement in PFS compared to P was observed in both R-pretreated and R-naïve pts, supporting the concept of continuous antiangiogenic therapy. A slight improvement in OS was observed in R-pretreated compared to R-naïve pts. Clinical trial information: NCT02149108.
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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 | 0.000 |
| 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) | 0.004 | 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".