Outcomes based on age in the phase 3 CELESTIAL trial of cabozantinib (C) versus placebo (P) in patients (pts) with advanced hepatocellular carcinoma (HCC).
Bibliographic record
Abstract
4090 Background: The incidence of HCC generally increases with age, although the age of onset varies depending on disease etiology and geographic region (Yang, Nat Rev Gastroenterol Hepatol 2010). In the phase 3 CELESTIAL trial (NCT01908426), C, an inhibitor of MET, VEGF receptors, and AXL, improved overall survival (OS) and progression-free survival (PFS) compared with P in pts with previously-treated advanced HCC. Overall, median OS was 10.2 mo for C vs 8.0 mo for P (HR 0.76, 95% CI 0.63–0.92; p = 0.0049), and median PFS was 5.2 mo for C vs 1.9 mo for P (HR 0.44, 95% CI 0.36–0.52; p < 0.0001). Here, we evaluate clinical outcomes based on age in the CELESTIAL trial. Methods: 707 pts were randomized 2:1 to receive C (60 mg qd) or P. Eligible pts had pathologic diagnosis of HCC, Child-Pugh score A, ECOG PS ≤1, and must have received prior sorafenib. Randomization was stratified by disease etiology, geographic region, and extent of disease. Outcomes were analyzed for subgroups based on age ( < 65 years and ≥65 years). Results: Median age at baseline was 64 years; 51% of pts were < 65 years old. Etiology of HBV was more frequent in pts < 65 years vs ≥65 years old (52% vs 22%), while etiology of HCV occurred at a similar frequency in both age groups (24%). Asian race and enrollment in Asia were more frequent in pts < 65 years vs ≥65 years old (46% vs 21% Asian race; 35% vs 14% enrolled in Asia). Median OS was 9.6 mo for C vs 7.7 mo for P (HR 0.81, 95% CI 0.62–1.05) for pts < 65 years old and 11.1 mo for C vs 8.3 mo for P (HR 0.74, 95% CI 0.56–0.97) for pts ≥65 years old. Median PFS was 5.0 mo for C vs 1.9 mo for P (HR 0.45, 95% CI 0.35–0.57) for pts < 65 years old and 5.4 mo for C vs 2.0 mo for P (HR 0.46, 95% CI 0.35–0.59) for pts ≥65 years old. The discontinuation rate due to treatment-related adverse events in the C group was lower in pts < 65 years vs ≥65 years old (11% vs 22%), while the percentage of pts with any dose reduction (61% vs 64%) and the median average daily dose of C (37 mg vs 34 mg) were similar in both age groups. The most common grade 3/4 adverse events in both age groups were consistent with those in the overall population. Conclusions: C improved OS and PFS vs P in pts with previously-treated advanced HCC irrespective of age category. Clinical trial information: NCT01908426.
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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 | 0.003 | 0.003 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.003 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.002 | 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".