Sequential hepatectomy for hepatocellular carcinoma with inadequate future-liver-remnant after portal vein ligation in combination with apatinib plus camrelizumab (PLACES): a single-arm prospective pilot study.

Background: The efficacy and safety of combining portal vein ligation (PVL) with apatinib and camrelizumab to make hepatocellular carcinoma (HCC) with insufficient future-liver-remnant (FLR) resectable are uncertain. This study aimed to explore the potential of PVL combined with systemic therapy in the treatment of HCC with insufficient FLR. Methods: In this single-arm, prospective phase II clinical trial (PLACES study), patients with HCC and inadequate FLR underwent initial PVL followed by apatinib and camrelizumab until they met the stage-II resection criteria. Post-hepatectomy, adjuvant therapy with apatinib and camrelizumab continued for one year. The primary endpoint was 1 year event-free survival (EFS) rate, defined as the time from phase I surgery to disease progression, postoperative recurrence, or death from any cause. Clinical profiles were compared to historical cases of associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) at the same center using propensity score matching (PSM). Results: Thirty patients were enrolled in the PLACES study. The objective response rate was 26.7% (8/30, RECIST v1.1) or 40% (12/30, mRECIST). Twenty-three (76.7%, 23/30) achieved sufficient FLR, and out of those, 20 (66.7%, 20/30) completed stage-II hepatectomy. The 1-year EFS rate in the PLACES group was found to be 63.3% [95% confidence interval (CI): 48.2-83.1%]. Twenty patients (66.7%, 20/30) experienced grade ≥3 treatment-related adverse events, with hypoalbuminemia being the most common (>50%). Fecal microbiological analysis suggested that Conclusions: PVL combined with apatinib and camrelizumab emerged as a promising therapy for HCC with inadequate FLR, demonstrating both efficacy and safety (chictr.org number, ChiCTR2000033692).