Findings from the study demonstrated that there were no significant differences in terms of EOL outcomes among patients who received an ICI as their final treatment vs those who received another approach. The numbers of hospice referrals (P = .31), palliative care referrals (P = .47), deaths in a hospital or facility (P = .86), documented goals-of-care discussions (P = .57), advance directive documentation (P = .68), and do-not-resuscitate/do-not-intubate instances (P = .81) were similar between both arms.
“We found that when we compared our primary EOL outcomes between patients with HCC who received immunotherapy compared with nonimmunotherapy as their last systemic therapy, there were surprisingly no differences,” Wheless wrote in an email to Oncology Fellows. “The biggest message from this study is that we as providers should be having iterative serious illness conversations with patients with any change in functional status, liver function, or hospitalization to ensure that patients’ EOL wishes are honored, but also that we as providers are using immunotherapy appropriately.”
Wheless is a fellow in the Division of Hematology/Oncology at Vanderbilt University Medical Center in Nashville, Tennessee.
Wheless noted that since the first approval in 2020, ICIs have revolutionized treatment for patients with HCC. Following the May 2020 FDA approval of atezolizumab (Tecentriq) plus bevacizumab (Avastin) in patients with unresectable HCC who have not received prior systemic therapy, tremelimumab-actl (Imjudo) plus durvalumab (Imfinzi), as well as nivolumab (Opdivo) plus ipilimumab (Yervoy), also received FDA approval in the frontline setting in October 2022 and April 2025, respectively.2-4
“We conducted this study because EOL and health care utilization outcomes are unknown in patients with HCC since the [initial] approval of immunotherapy in 2020,” Wheless explained. “The treatment landscape has drastically changed since 2020, but it was unknown how EOL and health care utilization outcomes are affected by the rapidly evolving treatment paradigm for patients with HCC. Studies in non-HCC solid tumors have shown increased treatment with ICIs near death in cancers that routinely use immunotherapy, such as melanoma or urothelial carcinoma.”
What was the design of the study, and what were the baseline characteristics?
To conduct their study, Wheless and her coauthors identified patients with HCC per International Classification of Diseases code in the electronic medical records of Vanderbilt between January 2020 and January 2024 and confirmed the diagnoses via manual chart review (n = 221).1 The study authors removed patients who were lost to follow-up (n = 33), those with non-HCC histology (n = 5), those who were still alive (n = 111), and duplicate patients (n = 1).
The primary outcomes were the EOL outcomes, including hospice and palliative care referrals, deaths in a hospital or facility, documented goals of care, advance directive documentation, and do-not-resuscitate/do-not-intubate instances. The secondary outcomes were receipt of systemic therapy, hospitalizations, intensive care unit (ICU) admission, and emergency department visits within 14, 30, and 90 days of death.
A total of 71 patients were included in the final cohort; the mean ages at diagnosis and last systemic therapy were 64.1 years (range, 35-83) and 64.2 years (range, 35-84), respectively. Patients received a median of 1 prior line of systemic therapy, and most (83.9%) received prior arterially directed therapy. Most patients did not undergo prior surgery for HCC (84.3%), did not receive a prior liver transplant (95.7%), and had Child-Pugh A5 disease at diagnosis (55.9%).
What were the additional findings presented during the Fellows Forum?
Further data from the retrospective study showed that among patients with available outcome data within 90 days of death (n = 33), 23 received an ICI. These patients experienced higher rates of emergency department visits, hospitalizations, and ICU admissions compared with those who received another treatment. These results were consistent within 30 and 14 days of death, although more patients received another treatment (n = 4) compared with an ICI (n = 2) at 14 days.
“When we examined our secondary outcomes, we found that more patients were receiving systemic therapy with immunotherapy within 90 and 30 days of death,” Wheless noted. “These patients also had increased health care utilization outcomes such as ICU admissions, hospital admissions, and emergency room visits within 90, 30, and 14 days of death.”
Wheless hopes to expand her research to include additional cancer centers and a more diverse patient population. She noted that it might be beneficial to include other scoring systems beyond Child-Pugh due to the heterogeneity of the cohort in her study. “This study highlights the need for prognostic risk stratification tools in patients with HCC receiving treatment with immunotherapy,” she said.
“The Fellow’s Forum was a great way to get to meet and interact with peers who have similar career goals and research interests as myself,” Wheless commented. “It was truly inspiring to listen to the current research my peers are doing and the type of research they have already done. The Fellow’s Forum provided a dedicated space for us to brainstorm research ideas, make connections, and make friends who may be collaborators or colleagues in the future.”
References
- Wheless M. End-of-life outcomes and healthcare utilization for patients with hepatocellular carcinoma who received immune checkpoint inhibition. Presented at: OncLive National Fellows Forum for Gastrointestinal Oncology; September 11, 2025; Austin, TX.
- FDA approves atezolizumab plus bevacizumab for unresectable hepatocellular carcinoma. FDA. Updated June 1, 2020. Accessed October 27, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-atezolizumab-plus-bevacizumab-unresectable-hepatocellular-carcinoma
- FDA approves tremelimumab in combination with durvalumab for unresectable hepatocellular carcinoma. FDA. Updated October 24, 2022. Accessed October 27, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-tremelimumab-combination-durvalumab-unresectable-hepatocellular-carcinoma
- FDA approves nivolumab with ipilimumab for unresectable or metastatic hepatocellular carcinoma. FDA. April 11, 2025. Accessed October 27, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-nivolumab-ipilimumab-unresectable-or-metastatic-hepatocellular-carcinoma
