Pembrolizumab and stereotactic radiotherapy combined in subjects with advanced HCC: A phase II study (PEMRAD).
Bibliographic record
Abstract
602 Background: Combination approaches of immune-checkpoint inhibitors and locoregional therapies have an increasing role in advanced HCC. Methods: The PEMRAD phase II trial investigated the efficacy of combination pembrolizumab and stereotactic body radiation (SBRT) following progression on sorafenib. Patients with advanced HCC, ECOG 0-1 and Childs-Pugh A were eligible. Patients received pembrolizumab on day 1 followed by SBRT starting Day 2 and delivered in five fractions. Pembrolizumab was continued every 21 days until progression, unacceptable toxicity or patient withdrawal. The primary endpoint was objective response rate (ORR) as measured by RECISTv 1.1. hypothesizing an increase to 40% with the combination. Tissue and liquid biopsies were collected for correlative analyses including multiplex IHC, longitudinal CyTOF and dynamic cytokine changes. Results: The trial was stopped early due to a shift in the treatment landscape. Between March 2018 and March 2023 18 patients of a planned 22 patients were enrolled and treated with combination therapy. Of these 10 (55%) had evidence of macrovascular invasion (MVI) and 15 (83%) had extrahepatic disease; viral hepatitis was the underlying etiology in 50%. The ORR was 41% meeting the proposed endpoint. Median number of cycles of pembrolizumab was 7.5 (2-35) .The median number of lesions treated by SBRT was 3 (1-5) and the median dominant gross tumour volume was 184 cc (IQR 69-285). The median PFS was 5.4 (2.8-9.9) months and median OS 12.6 (5.7-25.8) months. Of the 10 patients with macrovascular invasion 5 (50%) had evidence of a vascular thrombus response by RECIST criteria including 1 complete response. Treatment related adverse events ≥ grade 3 were reported in 5 patients (28%). One death due to myocarditis was attributed to treatment. Conclusions: In a poor prognostic group of patients in the second line setting, the combination of SBRT and pembrolizumab demonstrated high ORR and may have a specific role in patients with MVI. Correlative analyses will be presented at the meeting. Clinical trial information: NCT03316872 .
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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 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.001 | 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".