Abstract 957P
Background
So far there is no neoadjuvant therapy recommended by major hepatocellular carcinoma (HCC) guidelines. In other malignancies, ICIs in the neoadjuvant setting have shown better outcomes than in the adjuvant setting, and the combination of radiation therapy to ICIs incrementally improves the systemic response to ICIs. Neoadjuvant therapy of ICIs plus stereotactic body radiotherapy (SBRT) has shown promising results in several types of solid tumours but not HCC.
Methods
This is a phase Ib clinical trial of neoadjuvant SBRT plus PD-1 (tislelizumab) in HCC patients (pts). Prior to resection, pts receive 8 Gy × 3 SBRT with 2 cycles of PD-1. HCC resection is scheduled 4 weeks after the second PD-1, followed by adjuvant PD-1 for up to 1 year. We plan to enrol 20 participants in this trial. The primary study endpoints include the surgery delay over 6 weeks or later, ORR on pre-resection imaging, pathologic response (pCR) rate, safety and tolerability of the sequential SBRT/PD-1. The secondary endpoints are DFS and OS rates every 3 or 6 months after the hepatic resection.
Results
By 10th May 2023, 11 pts were enrolled, all were BCLC A stage. One pt was excluded due to the protocol violation, in other 10 pts, one just starts the adjuvant therapy, two have completed the neoadjuvant therapy and waiting for the scheduled resection, all other 7 pts have completed the resection, and no surgery delay accrued; DCR reached 100% (RECIST: 1 PR, 6 SD; mRECIST: 1 CR, 2 PR, 3 SD, 1 CR+SD ); pCR was confirmed in two tumors; So far the safety of neoadjuvant SBRT+PD-1 was satisfied, grade 1 to 2 TRAEs, mainly anemia and white blood cell decreasing were common; grade 3 TRAE occurred in 3 pts (1 granulocytopenia and 2 elevated transaminase), but all well-tolerated. One pt developed recurrence 9 months after surgery (RF ablation), all other 6 pts are still in DFS. Table: 957P
Pt # | age (Y) | gender | tumor size (cm) | BCLC stage | RECIST | mRECIST | interval between 2nd PD-1 and surgery | pCR (Y/N) | TARE over grade 3(Y/N) | survival |
1 | 70 | F | S7:2.4×2.2 | A | SD | SD | 31 | N | N | Recurrence/RFA |
2 | 74 | M | S4a:1.6; S2:1.2 | A | SD | S4a:CR; S2:SD | 28 | S4a: Y; S2:N | No | DFS |
3 | 64 | M | S8:1.8×1.6 | A | SD | SD | 28 | N | Y | DFS |
4 | 51 | M | S7/8:6.0×6.1 | A | PR | PR | 26 | Y | Y | DFS |
5 | 70 | M | S4/5:3.7×4.1 | A | SD | PR | 40 | N | N | DFS |
6 | 52 | M | S6/7:4.1×4.0 | A | SD | CR | 28 | N | Y | DFS |
7 | 70 | F | S6:3.3 | A | SD | SD | 34 | N | N | DFS |
8 | 48 | F | S8:2.2×1.7 | A | PR | CR | N | |||
9 | 56 | M | S6:2.9×2.4 | A | N | |||||
10 | 54 | M | S6:4.8×3.3; S8:2.2×1.8 | A | N |
Conclusions
The safety and clinical significance of radiotherapy plus PD-1 as the neoadjuvant therapy in HCC needs further exploration.
Clinical trial identification
NCT05185531.
Editorial acknowledgement
N/A
Legal entity responsible for the study
The authors.
Funding
The Key Research and Development Program of Shandong (Major Science & Technology Innovation Project), 2021SFGC0501. The reported trial is partly funded by BeiGene.
Disclosure
L. Zhao: Financial Interests, Personal, Speaker’s Bureau: Innovent, Hengrui Medicine, MSD, Roche, Bayer; Financial Interests, Personal and Institutional, Speaker’s Bureau. All other authors have declared no conflicts of interest.
Resources from the same session
842P - Multicenter real-world study of newly diagnosed advanced-stage extranodal natural killer/T cell lymphoma (ENKTL): Proposal for intensive therapy
Presenter: Yu-Ce Wei
Session: Poster session 18
844P - Progression -free survival prediction of multiple myeloma patients in five European countries using machine learning models
Presenter: Maria Luisa Pleguezuelo Witte
Session: Poster session 18
845P - A machine learning based clinical platform for cancer subtyping and data integration in hematological malignancies
Presenter: Michelle Tang
Session: Poster session 18
846P - Artificial intelligence-driven identification of onco-hematology patients who may develop severe COVID-19
Presenter: Souad Assaad
Session: Poster session 18
847P - Fatal infections among leukemia patients
Presenter: Huijie Zhou
Session: Poster session 18
848P - Mortality after rasburicase vs allopurinol anti-hyperuricemia monotherapy in patients with liquid tumors
Presenter: Mitchell Cairo
Session: Poster session 18
849P - Long non-coding RNA signatures and their role in the progression of childhood T cell acute lymphoblastic leukemia
Presenter: Pankaj Sharma
Session: Poster session 18
850P - A zebrafish model of MYC-driven acute myeloid leukemia reveals that neutrophil resistance to oncogenic transformation depends on their ability to promote PP2A-mediated MYC proteasomal degradation
Presenter: Anna Maria Luciano
Session: Poster session 18
851P - Characterization of a zebrafish model of MYC-driven acute myeloid leukemia
Presenter: Anna Maria Luciano
Session: Poster session 18
852P - c-MAF-driven metabolic reprogramming mediates H3K27 hyperacetylation to regulate super enhancer-associated genes
Presenter: Phyllis SY Chong
Session: Poster session 18