Patient-Level Analysis Explores Link Between Preoperative ICI Therapy, Improved Relapse-Free Survival for Hepatocellular Carcinoma

Immune checkpoint inhibitors (ICIs) are well-established as the standard of care for patients with unresectable or metastatic hepatocellular carcinoma (HC). While surgical procedures like liver resection can be curative for early-stage patients with HC, the relapse rate is high in the first five years post-resection.

To bridge this gap in care, a recent, first-of-its-kind analysis reviewed patient-level data to “describe the characteristics of pathological responses after preoperative ICI therapy in patients with hepatocellular carcinoma and to evaluate the association between the depth of tumor regression and relapse-free survival.”

Antonio D’Alessio, MD, of Imperial College London, and colleagues conducted a pooled analysis from patients around the world with HC receiving neoadjuvant ICI therapy before liver resection. The patients from these trials were part of a “global collective consortium (NeoHCC) of five phase I and II clinical trials and standardized observational protocols conducted in 12 tertiary referral centers across the USA, UK, and Taiwan.”

To gather the necessary data, the researchers searched PubMed for studies and patient cases that fit the eligibility criteria between January 1, 2020, and February 29, 2024. They focused on the characteristics of tumor regression and how it is associated with long-term survival outcomes, with the goal of “identifying the optimal threshold of pathological response associated with a reduced risk of relapse.”

Eligibility criteria for patients included being 18 years or older, a diagnosis of HC by “tissue core biopsy before treatment initiation,” a score of five on imaging using the Liver Imaging Reporting and Data System, a performance status score of zero to one using the standards of the Eastern Cooperative Oncology Group, and “no extrahepatic spread or previous ICI treatment.” The data cutoff was January 31, 2024.

Using the percentage of non-viable tumor from resected livers, the study authors categorized major pathological response (MPR) as showing at least 70% tumor regression and pathological complete response (PCR) as showing 100% tumor regression. Pathological response was correlated with “radiological overall response using RECIST criteria… and relapse-free survival.”

The study analyzed 111 patients who received treatment from October 5, 2017, to November 15, 2023. Sixty-nine percent of patients received ICI combinations “for a median of 1.4 months (IQR 0.7-2.9).” Sixty-six percent of patients had underlying viral chronic liver disease and 55% had Barcelona Clinic Liver Cancer stage A HC. Seventy-eight percent of those patients did not have portal vein thrombosis, and “87 (78%) patients were men and 24 (22%) were women.”

MPR was observed in 32% of patients and PCR was observed in 18% of patients. Seventy-four percent of patients with radiological response showed MPR compared to 14% of patients without radiological response (P<.0001), demonstrating that radiological overall response was associated with MPR. However, the study found that 30% of 33 patients showing MPR “were not predicted by radiological response.”

The study highlighted that “median relapse-free survival for the whole cohort was 43.6 months” after the median follow up point of 27.2 months. The researchers determined that “relapse-free survival was significantly longer in patients with major pathological response than in those who did not have a major pathological response (not reached [95% CI not evaluable – not evaluable] vs 28.3 months [12.8-43.8]; hazard ratio 0.26 [0.10-0.66]; P=.0024),” and the same was found for patients with PCR versus patients who did not have PCR (NR [95% CI not evaluable – not evaluable] vs 32.8 months [15.0-50.5]; 0.19 [0.05-0.78]; P=.010).

The researchers concluded the percentage of tumor regression after receiving neoadjuvant ICI therapy “could identify patients with improved relapse-free survival following liver resection.” They found that at least 90% tumor regression was the validation threshold for relapse-free survival in phase III randomized controlled trials.

Source: The Lancet Oncology