Clinical Edge Journal Scan

Commentary: Multifocal Hepatocellular Carcinoma, November 2022

Dr. Damjanov scans the journals, so you don’t have to!

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Nevena Damjanov, MD

Treatment of multifocal hepatocellular carcinoma (HCC) is challenging. This month, we will review articles that address the management of patients with more than one HCC lesion.

Orimo and colleagues addressed the use of liver resection in patients with more than one HCC in the liver. Patients with no or Child-Pugh A/B cirrhosis were included in this single-center retrospective study of 1088 patients who underwent hepatectomy for Barcelona Clinic Liver Cancer (BCLC) stage 0 (n = 88), A (n = 750), or B (n = 250) HCC, with stages A and B subcategorized into A1 (single nodule 2-5 cm or ≤ 3 nodules ≤ 3 cm), A2 (single nodule 5-10 cm), A3 (single nodule ≥ 10 cm), B1 (2-3 nodules > 3 cm), and B2 (≥ 4 nodules). The 5-year overall survival (OS) rates for stage 0, A1, A2, A3, B1, and B2 patients were 70.4%, 74.2%, 63.8%, 47.7%, 47.5%, and 31.9%, respectively (P < .0001). Significant differences in overall survival (OS) were found between stages A1 and A2 (P = .0118), A2 and A3 (P = .0013), and B1 and B2 (P = .0050), but not between stages A3 and B1 (P = .4742). In stage B1 patients, Child-Pugh B cirrhosis was the only independent prognostic factor for OS. The authors concluded that hepatectomy is beneficial in patients with three or fewer hepatocellular carcinomas and either no or Child-Pugh class A cirrhosis, with the long-term results being comparable to those in patients who underwent a resection of a single HCC. Therefore, resection of up to three HCC is safe and should be considered in clinically appropriate patients.

Many patients with multifocal HCC are not eligible for liver-directed therapies. The standard of care for first-line systemic therapy is the combination of atezolizumab and bevacizumab, as reported in the IMbrave150 clinical trial. Fulgenzi and colleagues published the results of a multicenter prospective observational study, AB-Real, that included 433 patients who received atezolizumab and bevacizumab in routine clinical practice. The investigators confirmed the efficacy of the combination and found that portal vein tumor thrombosis and worse albumin-bilirubin grade were independent prognostic factors for poor OS and were associated with an increased risk for hemorrhagic events. In addition, the authors reported that the overall response rate (ORR) predicted better outcomes, including longer OS. Therefore, atezolizumab and bevacizumab remains a safe and effective first-line treatment for many patients with unresectable HCC.

Finally, Finn and colleagues reported the results of an open-label, noncomparative cohort of the REACH-2 study of ramucirumab in 47 patients with advanced HCC and an alpha-fetoprotein (AFP) level ≥ 400 ng/mL. These patients had previously received one to two lines of systemic therapy, excluding sorafenib or chemotherapy. Lenvatinib was the most common prior systemic therapy (n = 20; 43%). Others included immune checkpoint inhibitor (CPI) monotherapies (n = 11), CPI/antiangiogenic therapy (n = 14), or dual CPI therapy (n = 5). The ORR was 10.6% (95% CI 1.8-19.5) and disease control rate was 46.8% (95% CI 32.5-61.1), with a median duration of response of 8.3 months [95% CI 2.4 to not reached). The grade 3 or more adverse event rate was 57%, with hypertension (11%) being the most common, allowing the authors to conclude that ramucirumab offers clinically significant efficacy with no new safety signals in this setting. Therefore, ramucirumab remains as a safe and effective later-line treatment option for patients with unresectable HCC and an AFP ≥ 400 ng/mL.

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