Neoadjuvant immunotherapy may broaden surgery eligibility for hepatocellular carcinoma
Click Here to Manage Email Alerts
Key takeaways:
- Neoadjuvant immunotherapy may help expand access to surgical resection for hepatocellular carcinoma.
- More research is needed to identify the best candidates for neoadjuvant immunotherapy.
Neoadjuvant immunotherapy may allow more people with hepatocellular carcinoma to undergo surgical resection, according to retrospective study results.
Patients with high-risk localized HCC who received neoadjuvant immune checkpoint inhibitors — including many who would have been ineligible for surgery based on traditional criteria — achieved similar RFS following surgery as patients who underwent upfront resection.
“We were very excited by these results,” Mari Nakazawa, MD, clinical research fellow at Sidney Kimmel Comprehensive Center at Johns Hopkins Medicine, told Healio. “What we consider traditionally ‘resectable’ in hepatocellular carcinoma may be too narrowly defined.”
Background and methods
HCC — the fifth leading cause of cancer death in the United States — accounts for 80% of primary liver cancer diagnoses., according to study background.
Only 30% of patients with HCC are eligible for upfront resection. Reasons for ineligibility include tumor size, location, extrahepatic or vascular extensions, and poor hepatic reserve.
Prior research has suggested neoadjuvant immunotherapy-based combinations can extend RFS for patients with high-risk HCC after resection.
“[Although] many of these studies have shown that this approach is feasible and that patients are able to successfully proceed to surgery, we do not know what their long-term outcomes are, and especially how they may compare with a cohort of patients who underwent upfront surgery,” Nakazawa said. “To answer this question, we retrospectively reviewed and analyzed patients over the last 5 years who received neoadjuvant immunotherapy followed by surgery, and those who received surgery alone.”
The cohort included 92 individuals (69.6% men; 57.6% white) with high-risk localized HCC who underwent liver resection at Johns Hopkins Hospital between Jan. 1, 2017, and Dec. 1, 2023.
More than one-third (39.1%; n = 36) received neoadjuvant immune checkpoint inhibitor therapy, and most (61.1%) of those patients would not have been eligible for upfront resection based on current criteria.
Patients in the neoadjuvant immunotherapy cohort had greater likelihood than those in the upfront surgery group to have higher-risk disease based on based on alpha-fetoprotein level (38.9% vs. 14.3%), tumors larger than 5 cm (72.2% vs. 37.5%), portal vein invasion (25% vs. 0%) and multiple tumor foci (50% vs. 12.5%).
Results and next steps
Results showed comparable RFS in the neoadjuvant immunotherapy and upfront surgery groups (44.8 months vs. 49.3 months).
Median OS had not been reached in either group.
Nearly all (94.4%) patients who received neoadjuvant immunotherapy underwent margin-negative resection.
“Our findings demonstrate that systemic therapy may not only be useful for patients with advanced disease but can potentially be paradigm changing [for] patients with early-stage disease,” senior author Mark Yarchoan, MD, associate professor of oncology at Sidney Kimmel Comprehensive Center at Johns Hopkins Medicine, said in a press release.
Researchers acknowledged study limitations, including its retrospective and single-institution nature, the small cohort and the potential that differences between the higher-risk patients who received neoadjuvant immunotherapy and lower-risk patients who underwent upfront surgery contributed to the lack of differences in clinical outcomes..
“There is a need to define which patients are the best candidates for neoadjuvant immunotherapy,” Nakazawa told Healio. “In addition to expanding the population of patients who might be able to undergo a curative surgery, neoadjuvant immunotherapy may also have a role [for] patients who are considered ‘resectable’ to prevent future recurrences, which is unfortunately common in HCC.
“Our results also show that the pattern of recurrence is different [among] patients who undergo neoadjuvant immunotherapy vs. upfront surgery — multifocal/distant vs. local recurrences, respectively — perhaps reflecting the presence of microscopic systemic disease in higher risk tumors, such as those who received neoadjuvant immunotherapy,” she added. “There are also questions surrounding the optimal duration of neoadjuvant therapy and whether adjuvant therapy ... should also be utilized. Altogether, there is a need to undertake thoughtfully designed prospective clinical trials in the right clinical populations addressing these questions.”
References:
- Nakazawa M, et al. Cancer Res Commun. 2024;doi:10.1158/2767-9764.CRC-24-0151.
- Neoadjuvant Immunotherapy may facilitate surgery and improve outcomes for patients with high-risk liver cancer (press release). Available at: https://www.aacr.org/about-the-aacr/newsroom/news-releases/neoadjuvant-immunotherapy-may-facilitate-surgery-and-improve-outcomes-for-patients-with-high-risk-liver-cancer/. Published Aug. 15, 2024; Accessed Aug. 15, 2024.
For more information:
Mari Nakazawa, MD, can be reached at mnakaza2@jhmi.edu.
Collapse
Click Here to Manage Email Alerts