When given neoadjuvant cemiplimab, 20% of hepatocellular carcinoma (HCC) patients experience a tumour necrosis of 70% or more, according to a phase IIa study of 21 patients with the disease, presented recently at the American Association for Cancer Research annual meeting.
The first line treatment for early-stage HCC is surgical resection of the tumour. However, despite negative margins and the apparent successful, full resection of the tumour, disease relapse is common. This may be due to residual disease or the presence of micro-metastases. Regardless, it is hoped that a neoadjuvant strategy may offer these patients better outcomes. Investigating the anti-PD-1 monoclonal antibody cemiplimab in this neoadjuvant setting, this study enrolled 21 early-stage HCC patients to receive cemiplimab (350mg intravenously every 3 weeks for 2 cycles), followed by surgery, receiving a further 8 cycles of cemiplimab to the same dosing schedule. Importantly, patients who had received treatment within 6 months, or who had undergone major surgery within 14 days of enrolment were excluded. The primary endpoint of this study was significant tumour necrosis (≥70% tumour necrosis), with secondary endpoints of delay of surgery, disease-free survival, overall response rate, overall survival adverse events and change in lymphocyte infiltration.
Patients enrolled in this study had a median age of 68 years of age, with 85.7% being male. 52.4% were of Asian descent and 85.7% had an ECOG performance score of 0. The primary endpoint of this study was met, reporting that 4 out of 20 patients experienced significant tumour necrosis. Additionally, 15% (N=3) patients experienced a pathological complete response (tumour necrosis of 100%). A further 35% (N= 7) experienced a tumour necrosis of at least 50%. One patient was intra-operatively aborted after the finding of metastases during the procedure. Adverse events were also manageable. 28.6% (N= 6) of patients experienced grade ≥3 treatment-emergent adverse events (TEAEs), with the most common being increased blood creatine phosphokinase (9.5%, N= 2), increased aspartate aminotransferase (4.8%, N= 1) and hypoalbuminaemia (4.8%, N= 1). The most common any-grade TEAEs were increased aspartate aminotransferase (28.6%, N= 6), increased alanine aminotransferase (14.3%, N= 3) and fatigue (14.3%, N= 3).
“This is the largest trial reported to date of neoadjuvant PD-1 targeted monotherapy in HCC,” said Dr. Thomas Marron, lead study author. “Pathological response data support larger trials to identify optimal clinical endpoints that correlate with improvement in survival, and to establish the utility and safety of perioperative PD-1 blockade.”
Marron T et al., Neoadjuvant cemiplimab demonstrates complete pathological responses in hepatocellular carcinoma. Presented at AACR Annual Meeting 2021; Abstract CT182.