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TOPLINE:

Neoadjuvant immunotherapy in high-risk patients with hepatocellular carcinoma (HCC) led to similar recurrence-free survival (RFS) and margin-negative resection rates compared with patients undergoing upfront surgery. The study highlights the potential of immunotherapy to expand surgical candidacy in patients with traditionally unresectable HCC.

METHODOLOGY:

• Only about 30% of patients diagnosed with HCC meet the eligibility criteria for surgical resection according to established guidelines. Among those who do have curative surgery, long-term outcomes are generally poor, as most patients experience a recurrence of the disease within 5 years of surgery.
• Researchers examined the outcomes of patients who underwent liver resection for HCC, comparing those who received neoadjuvant immunotherapy with those who had upfront resection at Johns Hopkins Hospital in Baltimore between January 1, 2017, and December 1, 2023.
• A total of 92 patients were included in the clinical cohort, with 36 receiving neoadjuvant immune checkpoint inhibitor-based treatment instead of upfront surgery. Of those who received neoadjuvant immunotherapy, the majority were treated with anti–programmed cell death protein 1-based therapy, either as monotherapy (27.8%), in combination with a tyrosine kinase inhibitor (36.1%), or in combination with an anti-lymphocyte activation gene 3 protein (16.7%).
• Most patients (61.1%) who received neoadjuvant immune checkpoint inhibitor-based therapy did not meet the standard criteria for resectability and exhibited characteristics that increase the risk for disease recurrence, such as alpha-fetoprotein levels of ≥ 400 ng/mL, tumors measuring ≥ 5 cm, evidence of portal vein invasion, and multifocal tumors.
• The primary endpoints were RFS (defined as the time from curative intent hepatectomy to radiographic disease recurrence or death) and overall survival.

TAKEAWAY:

• Compared with those who underwent upfront surgical resection, patients who received neoadjuvant immunotherapy had similar rates of successful margin-negative resection — 94.4% vs 87.5% for upfront surgery (P = .47).
• Patients who received neoadjuvant immunotherapy also had similar RFS compared with those who had upfront surgery — a median of 44.8 months vs 49.3 months, respectively (log-rank P = .66).
• The median overall survival was not reached in either cohort.
• In patients who received neoadjuvant immunotherapy and did not undergo liver-directed local therapy afterward, 30.3% exhibited a major pathologic response at the time of surgery, defined as tumor necrosis ≥ 70%. In comparison, 18.2% had a minor pathologic response (necrosis 30%-69%), while 51.5% had no pathologic response (necrosis 0%-29%).

IN PRACTICE:

Researchers acknowledged that surgical reduction for HCC is primarily reserved for solitary tumors without vascular invasion, but "neoadjuvant immunotherapy may allow high-risk patients, including those who are outside of standard resection criteria, to undergo successful margin-negative resection and achieve comparable long-term clinical outcomes compared to upfront resection."

SOURCE:

The study was led by Mari Nakazawa, Mike Fang, and Mark Yarchoan at the Johns Hopkins University School of Medicine in Baltimore. It was published online on August 15 in Cancer Research Communications.

LIMITATIONS:

The retrospective study design may introduce selection bias, as patients were not randomly assigned to treatment groups. The small sample size may limit the generalizability of the findings to broader populations. Additionally, the study was conducted at a single institution. The lack of long-term follow-up data limits the ability to assess the impact of neoadjuvant immunotherapy on overall survival.

DISCLOSURES:

Mark Yarchoan disclosed receiving grants from the National Cancer Institute and the Johns Hopkins Bloomberg-Kimmel Institute for Cancer Immunotherapy. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.