Pembrolizumab (pembro) vs placebo (pbo) in patients (pts) with advanced hepatocellular carcinoma (aHCC) previously treated with sorafenib: Updated data from the randomized, phase III KEYNOTE-240 study.
Bibliographic record
Abstract
268 Background: KEYNOTE-240 (NCT02702401) examined the anti-PD-1 antibody pembro and demonstrated improvement in OS and PFS vs pbo in pts with aHCC previously treated with sorafenib. However, the study did not meet prespecified statistical significance criteria for OS and PFS. Median OS (final analysis) was 13.9 mo for pembro vs 10.6 mo for pbo (HR 0.781; 95% CI 0.611-0.998). At the first interim analysis when PFS and ORR were prespecified to be tested, median PFS was 3.0 mo for pembro vs 2.8 mo for pbo (HR 0.775; 95% CI 0.609-0.987) and ORR was 16.9% (CR, n = 3) for pembro and 2.2% (CR, n = 0) for pbo. AEs were consistent with the known safety profile of pembro. Longer-term data from KEYNOTE-240 after ~1.5 years of additional follow-up are reported. Methods: Adults with confirmed aHCC who experienced failure (progression or intolerance) to sorafenib therapy were randomized 2:1 to pembro 200 mg IV Q3W + best supportive care (BSC) or pbo + BSC for ≤35 cycles or until confirmed progression/unacceptable toxicity, pt withdrawal of consent, or investigator decision. Dual primary end points were OS and PFS, assessed by blinded independent central review (BICR) per RECIST v1.1. Secondary end points included ORR, DOR, DCR, TTP (all assessed by BICR per RECIST v1.1), and safety. Results: Of 413 pts, 278 were randomized to pembro and 135 to pbo. As of July 13, 2020, median time from randomization to data cutoff was 39.6 mo (range 31.7-48.8) for pembro and 39.8 mo (31.7-47.8) for pbo. Median OS was 13.9 mo (95% CI 11.6-16.0) for pembro and 10.6 mo (8.3-13.5) for pbo (HR 0.771; 95% CI 0.617-0.964). Estimated OS rates at 24 and 36 mo for pembro and pbo were 28.8% and 20.4% and 17.7% and 11.7%, respectively. Median PFS was 3.3 mo (95% CI 2.8-4.1) for pembro and 2.8 mo (1.6-3.0) for pbo (HR 0.703; 95% CI 0.559-0.885). Estimated PFS rate at 24 mo was 11.8% for pembro and 4.8% for pbo. ORR was 18.3% (95% CI 14.0-23.4) for pembro and 4.4% (1.6-9.4) for pbo. Median time to response was 2.7 mo (95% CI 1.2-16.9) for pembro and 2.9 mo (1.1-6.9) for pbo. Median DOR was 13.9 mo (range 1.5+ to 41.9+) for pembro and 15.2 mo (2.8-21.9) for pbo; 45.1% of responders in pembro arm and 33.3% of responders in pbo arm had DOR ≥12 mo. DCR was 61.9% for pembro and 53.3% for pbo. Best overall responses were 10 CR, 41 PR, 121 SD, and 85 PD for pembro and 0 CR, 6 PR, 66 SD, and 54 PD for pbo. The median TTP was 4.0 mo (95% CI 2.8-5.3) for pembro and 2.8 mo (1.6-3.0) for pbo. No new or unexpected AEs occurred. The frequency of sponsor-assessed immune-mediated hepatitis events did not increase with additional follow-up. There continued to be no HBV or HCV viral flare events. Conclusions: In previously treated pts with aHCC, improvement in OS and PFS was maintained over time with pembro vs pbo, and the safety profile remained consistent over time. These data support the benefit:risk profile of pembro. Clinical trial information: NCT02702401.
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 | 0.002 | 0.002 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.003 | 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".