Updated efficacy and safety of KEYNOTE-224: A phase II study of pembrolizumab (pembro) in patients with advanced hepatocellular carcinoma (HCC).
Bibliographic record
Abstract
518 Background: Pembro received accelerated approval in pts with advanced HCC in the second-line setting based on results of the KEYNOTE-224 trial. Results of a 2 y follow-up analysis of the efficacy and safety in this trial are presented here. Methods: Eligible pts had histologically confirmed HCC, radiographic progression on/intolerance to sorafenib and disease not amenable to curative treatment, Child Pugh A, ECOG PS 0-1 and BCLC stage C or B. Pts received pembro 200 mg IV Q3W for 2 y or until disease progression, unacceptable toxicity, consent withdrawal or investigator decision. Response was assessed every 9 wk. Primary endpoint was ORR (RECIST v1.1, central review). Secondary endpoints were DOR, DCR, PFS, OS and safety. Results: Efficacy and safety were assessed in 104 pts. The median time from randomization to data cutoff (Jun 05, 2019) was 31.2 mo (27.5-35.5 mo). Pt characteristics were: median age 68 y (43-87), 21.2% HBV+, 25% HCV+, 94.2% Child Pugh A, 79.8% had PD on sorafenib, 17.3% had MVI and 64.4% had extrahepatic disease. ORR was 18.3% (95% CI 11.4-27.1) and was similar across subgroups. Median DOR was 21.0 mo (3.1-28+ mo); 77% had responses lasting ≥12 mo (Kaplan Meier). Best overall responses were 4 (3.8%) CRs, 15 (14.4%) PRs, 45 (43.3%) SDs and 34 (32.7%) PDs; DCR was 61.5%. The median PFS (95% CI) was 4.9 mo (3.5-6.7) and OS was 13.2 mo (9.7-15.3). PFS 24 mo rate was 11.3% and OS 24 mo rate was 30.8%. ORR was shown to be a predictor of longer OS by landmark analysis. Treatment-related AEs occurred in 76 (73.1%) pts; the most common AEs were fatigue, increased aspartate aminotransferase, pruritus and diarrhea observed in ≥10% pts. Grade ≥3 treatment related AEs occurred in 27 (26.0%) pts. Immune-mediated hepatitis occurred in 3 (2.9%) pts; no cases of HBV/HCV flare were identified. Conclusions: At 2 y follow-up, pembro continued to provide durable anti-tumor activity and prolonged survival (30.8% OS, 24 mo rate), further supporting its use in previously treated pts with advanced HCC. With longer follow-up, increases in ORR (18.3% vs 17.0%), DOR ≥12 mo (77.0% vs 61.4%) and CR rates (3.8% vs 1%) were seen. The safety profile was similar to the primary analysis. Clinical trial information: NCT02702414.
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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 | 0.002 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| 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".