Posted: Wednesday, May 17, 2023
The selective anti–PD-1 antibody sintilimab plus gemcitabine and cisplatin appeared to be safe and active as a first-line treatment in patients with advanced biliary tract cancer, according to Zhen-gang Yuan, MD, of the Eastern Hepatobiliary Surgery Hospital, Shanghai, and colleagues. The findings of a phase II trial, which were published in Nature Communications, offer a potential treatment option and lay the groundwork for further investigation of this regimen. Sintilimab has been approved in China in the treatment of Hodgkin lymphoma and hepatocellular carcinoma.
“Many novel chemotherapy agents have presented modest efficacy, but the overall benefits are still limited,” the investigators commented. “Hence, there is an urgent requirement to develop other treatment options.”
A total of 30 patients were treated with sintilimab plus gemcitabine and cisplatin. Most of them (28 of 30; 93.3%) had intrahepatic cholangiocarcinoma found as the primary tumor type. A total of 25 of the 30 patients (83.3%) has metastatic disease.
The median durations of overall and progression-free survival were 15.9 and 5.1 months, respectively. The objective response rate was 36.7%. Thrombocytopenia (33.3%) was the most frequently reported grade 3 or 4 treatment-related adverse event; according to the investigators, there were no deaths nor unexpected safety events.
A predefined biomarker analysis revealed that patients with homologous recombination repair pathway gene alterations or loss-of-function mutations in chromatin remodeling genes experienced improved tumor response and survival outcomes. Based on a transcriptome analysis, higher objective response rates and longer durations of progression-free survival were associated with higher expression of a 3-gene effector T-cell signature and an 18-gene inflamed T-cell signature.
“Multiomics potential predictive biomarkers are identified and warrant further verification,” the investigators concluded.
Disclosure: For full disclosures of the study authors, visit ncbi.nlm.nih.gov.