This multicenter, prospective, randomized, controlled, open-label, two-arm Phase III clinical trial is designed to evaluate whether adding radiotherapy to oligoprogressive lesions while continuing first-line systemic therapy at the time of oligoprogression can effectively prolong progression-free survival compared to early switching to second-line systemic therapy in oligoprogressive hepatocellular carcinoma.
1. Histological or cytological confirmation of primary hepatocellular carcinoma (HCC), or diagnosis based on the Clinical Diagnosis and Treatment Guidelines for Primary Liver Cancer (2024 edition) issued by the National Health Commission of the People's Republic of China.
2. BCLC stage C at the time of first-line systemic treatment.
3. Oligoprogression must be confirmed by imaging or histopathology during first-line systemic therapy (FLST). The number of oligoprogressive lesions is limited to 1-5, involving no more than 1-3 organs or systems. These lesions may represent either new metastatic sites or progression of pre-existing lesions. In addition, they must fit one of the two classifications defined in the ESTRO-EORTC consensus on oligometastases: repeat oligoprogression or induced oligoprogression. Oligoprogression may occur within intrahepatic lesions. In the case of lymph node progression, each lymphatic drainage region is considered a separate lesion. For example, the para-aortic lymph nodes (number 16a and number 16b) are each counted as separate lymph node regions.
4. Patients must have experienced oligoprogression while receiving their current FLST and must not have previously received any other FLST that resulted in disease progression. Additionally, the current FLST must have maintained disease stability (SD) for at least three months prior to the occurrence of oligoprogression. Furthermore, the expected survival time must be ≥6 months.
1. Patients who received FLST as adjuvant treatment after curative surgery for HCC.
2. Tumor progression occurring within 3 months after initiation of FLST.
3. Patients with combined hepatocellular-cholangiocarcinoma (cHCC-CC)
4. History of grade ≥3 serious adverse events due to FLST.
Parallel
radiotherapy
RadiationRadiotherapy (Biologically Equivalent Dose \[BED\]≥60Gy)
Systemic therapy (Continuation of current first-line systemic therapy)
DrugContinuation of current first-line systemic therapy, which may include, but is not limited to, combinations such as atezolizumab plus bevacizumab, tremelimumab plus durvalumab, or monotherapies such as lenvatinib, sorafenib, tislelizumab, durvalumab, or pembrolizumab, at the discretion of the treating physician.
Systemic therapy (Early switch to second-line systemic therapy)
DrugFor patients who received sorafenib as FLST, regorafenib will be the preferred second-line option. For patients who received other FLST regimens, the SLST selection will be determined through an MDT discussion led by the treating physician based on the patient's overall condition, prior therapies, drug indications, and potential adverse effects, ensuring an individualized treatment approach. The specific dosing regimen, administration frequency, and dose adjustments will strictly follow the same prescribing information for each drug.
Progression-free survival (PFS)
The time between enrollment and disease progression or death for patients in the intent-to-treat population, whichever occurred first; for those who did not progress at the time of withdrawal from the study or whose time to disease progression was not recorded, the date of the last visit was used as the endpoint date.
Overall survival (OS)
Defined as the time from initiation of treatment to death from any cause.
Adverse event incidence (Safety)
Treatment-related adverse events are graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0 (CTCAE 5.0).
Objective response rate (ORR)
Defined as the proportion of patients whose tumor size decreases (partial response) or disappears (complete response) after radiation based on RECIST 1.1.
Disease control rate (DCR)
Defined as the proportion of patients whose tumor size decreases (partial response), disappears (complete response), or is stable after radiation based on RECIST 1.1.
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