Hepatocellular carcinoma (HCC) patients with major vascular invasion (MVI) were generally recommend systemic treatment by guidelines, while some data showed R0 resection can improve survival than local treatment. Conversion therapy using immune checkpoint inhibitors may benefit these patients in the context of cancer immunotherapy. Here we report a prospective real-world study of PD-1 inhibitors in combination with tyrosine kinase inhibitors (TKIs) as a conversion therapy for HCC with MVI.
Briefly, the main inclusion criteria of the study (ChiCTR1900023914) was: Aged 18 to 75 years HCC patients diagnosed pathologically and/or radiologically, with at least one measurable lesion (mRECIST) and MVI. The criteria for Successful Conversion: 1. Child-Pugh score < 7. 2. ECOG PS score ≤1. 3. No extrahepatic lesion. 4. Intact vascular structure of the reserved liver and sufficient FLR.
70 Patients were screened, and 39 patients enrolled in the study by May 20, 2020. Among them 35 patient accepted the combination therapy (Primary HCC n=31, Recurrence after local treatment n=4), in which 30 patients with PVTT, 2 with venous tumor thrombi and 3 with both. A total of 33 patients were assessable. The response evaluation according to mRECIST standard was in table below. Successful conversion rate based on radiology was 42.4% (14/33). Summary of response evaluation and conversion rate
Best objective response, n Total, n CR n=5 PR n=10 SD n=12 PD n=6 33 Successful Conversion, n 5 7 1 1 14 Reasons for not conversion Inadequate FLR n=2, Poor CTP n=1 Inadequate FLR n=11 Inadequate FLR n=5 Patients underwent subsequent surgery, n 4 3 1 1 9 Pathological evaluation of response pPR: 1/4 pPD: 2/3 pSD pPD
The subsequent salvage surgery was all en-bloc R0 resection of both tumor and PVTT. No complications beyond Clavien-Dindo level III or postoperative mortality were observed. The median follow-up time was 7.2 months. The median relapse free survival and median overall survival was 3.9 months and 6.5 months respectively. Patients with pPD had a worse prognosis.
The combination therapy of PD-1 inhibitors and TKIs can be reviewed as a reasonable and promising conversion therapy option for advanced HCC with safety and effectiveness. Furthermore, pathology can confirm the response evaluation and guide subsequent treatment more precisely.
ChiCTR1900023914.
The authors.
Has not received any funding.
All authors have declared no conflicts of interest.