Neoadjuvant Cemiplimab Induces Tumor Necrosis in Resectable HCC

Neoadjuvant cemiplimab-rwlc (Libtayo) induced significant tumor necrosis in patients with early-stage hepatocellular carcinoma (HCC) who underwent liver resection, said Parissa Tabrizian, MD, MSc, who added that the pathological response data warrant further evaluation of neoadjuvant immunotherapy in larger clinical trials in this patient population.

During week 1 of the 2021 AACR Annual Meeting, findings from an ongoing phase 2a open-label, multicohort trial (NCT03916627) were presented in a virtual poster. The results demonstrated that greater than 70% tumor necrosis was achieved in 20% (n = 4) of patients with resectable HCC following neoadjuvant cemiplimab. Moreover, 15% (n = 3) of patients achieved complete tumor necrosis. Finally, 35% (n = 7) of patients achieved tumor necrosis of 50% or greater.

As neoadjuvant therapy, cemiplimab, an IgG4 monoclonal antibody targeted toward PD-1, demonstrated a tolerable safety profile in this patient population.

“Based on these findings, there is value in incorporating [cemiplimab into the treatment of] patients who are candidates for surgery and have early-stage disease,” said Tabrizian, an author of the study. “Perhaps, also using this concept in patients who may have aggressive tumor biology and are borderline resectable [is reasonable]. Patients [who underwent transplant] or who are on the [transplant] waitlist and obtaining bridge therapies [could also benefit from cemiplimab].”

In an interview with OncLive®, Tabrizian, an assistant professor of surgery at Mount Sinai School of Medicine and a surgeon at the Recanati/Miller Transplantation Institute at Mount Sinai Hospital, discussed the rationale for evaluating cemiplimab in the neoadjuvant setting for patients with resectable HCC, the results of the trial, and next steps planned to identify optimal clinical end points that correlate with survival benefit.

OncLive®: What unmet need could utilizing immunotherapy in the neoadjuvant setting fulfill for patients with resectable HCC?

Tabrizian:The recommended first-line treatment for any [patient with] early-stage HCC is surgery, either in the form of [liver] resection or transplant. Unfortunately, despite [our best] efforts, recurrence [rates] remain high; [recurrence] has been seen in up to 50% to 70% [of patients] after resection and up to 10% to 15% [of patients] after transplant. Despite having negative margins in the majority of cases, we do believe that HCC recurs as a result of micrometastatic disease.

There may be rationale for using immunotherapy prior to surgery in order to decrease recurrence rates and achieve better outcomes. No standard, recommended [neoadjuvant] treatments [are available for patients with HCC] to date. This is why we felt that [we should] proceed with this trial [evaluating neoadjuvant cemiplimab].

What methods were utilized to evaluate cemiplimab in this setting, and what patients were included in the study population?

We used cemiplimab, which is an IgG4 monoclonal antibody against PD-1, in patients who were eligible for curative resection and had early-stage HCC. [Cemiplimab] has been approved for numerous cancers, including a subset of metastatic basal cell carcinoma and a subset of non–small cell lung cancer. We have tried to mimic [the results seen with cemiplimab in those tumor types] in our HCC cases.

[Eligible] patients were treated with [cemiplimab] at 350 mg every 3 weeks intravenously for 2 cycles prior to resection. Patients were treated subsequently with an additional 8 cycles [of cemiplimab] after surgery. Prior to surgery, we obtained tissue biopsy, blood work, and imaging. After the 2 cycles [of cemiplimab] we repeated imaging. An extensive tissue analysis was performed after surgery.

We included adults over the age of 18 years with good performance statuses and adequate organ and bone marrow function. The patients who we excluded had [undergone] organ transplant or major surgery prior to treatment start, or were immunocompromised. [Patients could not have] had any anticancer treatment within 6 months of entering the study.

What were the key findings of the research?

The primary end point was essentially looking at who had pathologic responses. We had secondary outcomes as well, such as disease-free survival [(DFS) and] overall survival [OS].

Our main finding was that 20% of the cohort [had] significant necrosis of over 70% following the neoadjuvant protocol. Three patients or 15% [of the cohort achieved] complete pathologic necrosis. [About] 35% of patients had 50% [or more] tumor necrosis.

Also, we looked at the adverse effects [AEs] on treatment. [The] safety-risk profile was acceptable in these patients. The most common AEs were elevated liver enzymes, fatigue, and gastrointestinal symptoms, but we felt that these were acceptable during treatment.

Are there any next steps planned to further evaluate neoadjuvant cemiplimab in this patient population?

Absolutely. This is an exciting time; immunotherapy has really reshaped liver cancer treatment. We can use our outcomes and enroll larger trials in order to confirm [these results] and look into OS and DFS to comment on whether this [regimen] will affect overall outcomes. We are trying to enroll more patients and establish a larger trial, but also look at treatment-naïve patients. Perhaps [we can] study combination treatments, as well, prior to surgery to see whether we can optimize outcomes [for patients] given our findings.

What do you hope your colleagues take away from this research?

It is an exciting time [for HCC research]. There is a strong rationale to incorporate immunotherapies earlier on in the treatment process. I hope that our results will affect the OS and DFS in this cohort of patients and continue to improve recurrence rates.

Reference

Marron T, Gunasekaran G, Tabrizian P, et al. Neoadjuvant cemiplimab demonstrates complete pathological responses in hepatocellular carcinoma. Presented at: 2021 AACR Annual Meeting; April 9-14, 2021; virtual. Poster: CT182. https://bit.ly/3wqnjXt.