The Efficacy of Combined Cisplatin and Nanoparticle Albumin-Bound Paclitaxel in a Stage IV Pancreatic Squamous Cell Carcinoma Patient With a Somatic BRCA2 Mutation: A Case Report

Abstract

Pancreatic squamous cell carcinoma (SCC) is a rare primary pancreatic malignancy with a poor prognosis. The median overall survival (OS) for metastatic setting is only 4 months and the optimal management remains poorly defined. In the present study, we report a 52-year-old female patient with stage IV primary SCC of the pancreas harboring a deleteous BRCA2 somatic mutation. After 10 cycles of chemotherapy of cisplatin combined with nanoparticle albumin-bound paclitaxel, metastatic lesions in the liver and lymph nodes achieved radiographic complete responses and pancreatic lesion shrank from 5.7 to 1.5 cm in diameter. The patient subsequently underwent a posterior radical antegrade modular pancreatosplenectomy with R0 resection and residual liver lesions were also resected. After 3 months, a tumor relapsed in the liver. She was then treated with olaparib combined with pembrolizumab and achieved stable disease on the liver lesion. The patient eventually died from cerebral hemorrhage with a long OS of 21 months. Our case demonstrated a favorable clinical activity and survival advantage of the combined cisplatin and nanoparticle albumin-bound paclitaxel, which might serve as a therapeutic option for the patient with BRCA-mutant pancreatic SCC.

Serum albumin binding knob domains engineered within a VH framework III bispecific antibody format and as chimeric peptides

“…Binding to serum albumin capitalises on the interaction of albumin with the neonatal Fc receptor (FcRn), which salvages gamma immunoglobulins and serum albumin from lysosomal catabolism thereby conferring a substantial half-life extension to both proteins (12,13). This approach has been used in a range of FDA approved peptide drugs, including the albumin-binding small molecule paclitaxel (14) and the glucagon-like peptide-1 agonist semaglutide, which contains an albumin-binding fatty acid moiety (15).…”

The proximity of the N- and C- termini of bovine knob domains enable engineering of target specificity into polypeptide chains

“…Notable Food and Drug Administration-approved examples include an interferon alpha-albumin fusion protein (albinterferon Alfa-2B, for chronic hepatitis C); 12 the glucagon-like peptide-1 agonist semaglutide, which contains an albumin-binding fatty acid moiety, 13 (Rybelsus®, for diabetes); 14 and the albumin-binding small molecule paclitaxel (Abraxane®, for pancreatic cancer). 15 When engineering albumin fusion proteins, the C-terminus has been shown to be required for FcRn binding 16 and in this study we present routes to engineer antigen specificity into albumin, independently of the termini.…”

Case Report: A complete pathologic response in pancreatic cancer with squamous cell differentiation

“…Huang et al. published a case report of a patient with stage IV pancreatic SCC with somatic Breast cancer 2 genes mutation, treated with cisplatin and nanoparticle albumin-bound paclitaxel ( 14 ). Similarly, the phase 1b/2 pilot clinical trial by Jameson et al.…”

“…Huang et al published a case report of a patient with stage IV pancreatic SCC with somatic Breast cancer 2 genes mutation, treated with cisplatin and nanoparticle albumin-bound paclitaxel (14). Similarly, the phase 1b/2 pilot clinical trial by Jameson et al shows a high overall response rate in patients with advanced pancreatic cancer treated with a triple regimen of cisplatin and albumin-bound paclitaxel plus gemcitabine (15).…”