Libtayo effective in killing HCC tumors prior to resection
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Neoadjuvant immunotherapy Libtayo administered before surgical resection led to tumor necrosis in about one-third of patients with hepatocellular carcinoma, according to data published in The Lancet Gastroenterology and Hepatology.
“The primary endpoint of the study was significant tumor necrosis, and we demonstrated that roughly a third of patients had significant necrosis after only 3 weeks of immunotherapy (so minimal delay of surgery),” senior author Thomas U. Marron, MD, PhD, director of the Early Phase Trials Unit at The Tisch Cancer Institute and associate professor of hematology and medical oncology at the Icahn School of Medicine at Mount Sinai, told Healio. “We hypothesize that — as has been seen in breast and lung — this will correlate with lower risk of recurrence. Recurrence-free survival is the primary goal following surgery for any cancer, in particular here, given the high risk of recurrence in HCC.”
Marron and colleagues enrolled 21 patients with resectable HCC (stage Ib, II, and III b) to participate in a single-arm, open-label, phase 2 trial. Patients received two cycles of 350 mg neoadjuvant Libtayo (cemiplimab; Regeneron Pharmaceuticals, Sanofi), an anti-PD-1 monotherapy, intravenously every 3 weeks before surgery. After resection, patients received another eight cycles of 350 mg cemiplimab intravenously every 3 weeks as adjuvant therapy.
Researchers identified significant tumor necrosis on pathological examination (defined as less than 70% necrosis of the resected tumor) as the primary endpoint of the study. Other endpoints included delay of surgery, the proportion of patients with an overall response, change in CD8+ T-cell density and adverse events. Marron and colleagues assessed tumor necrosis and response in patients who received at least one dose of cemiplimab and completed surgical resection; they also evaluated safety and other endpoints in the intention-to-treat population. Throughout treatment, patients underwent pre-treatment biopsies and blood collection.
Investigators noted 35% of patients after surgical resection achieved 50% or greater tumor necrosis.
According to study results, 20 patients experienced successful resection. Of those, four had significant tumor necrosis, three had a partial response and all other patients maintained stable disease. Researchers reported that 20 patients had treatment-emergent adverse events of any grade during the neoadjuvant treatment period, including increased aspartate aminotransferase, increased blood creatine phosphokinase, constipation and fatigue. Marron and colleagues also found that seven patients experienced grade 3 adverse events of increased blood creatine phosphokinase and hypoalbuminemia. No grade 4 or 5 events were noted, and only one patient developed pneumonitis, which delayed surgery by 2 weeks.
“We are currently analyzing biospecimens to identify potential biomarkers of response,” Marron told Healio. “Larger studies are needed to confirm that pre-operative immunotherapy can decrease the risk of recurrence, and whether there are good predictive biomarkers that could be used to identify these patients.”
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Marron T, et al. Lancet Gastroenterol Hepatol. 2022;doi:10.1016/S2468-1253(21)00385-X.
Immunotherapy before liver cancer surgery can kill tumor, and likely residual cancer cells. https://www.newswise.com/articles/immunotherapy-before-liver-cancer-surgery-can-kill-tumor-and-likely-residual-cancer-cells. Published Jan. 19, 2022. Accessed Jan. 19, 2022.
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