Abstract B05: Paclitaxel protein bound plus gemcitabine plus cisplatin and paricalcitol neoadjuvant therapy for localized pancreatic ductal adenocarcinoma (PDAC)

Background: Localized PDAC management has recently evolved. Due to concerns over micrometastases at diagnosis, the use of neoadjuvant chemotherapy for PDAC has become more common. Typical therapies involve the use of multiagent systemic chemotherapy with or without radiation therapy. Cancer antigen 19-9 (CA 19-9) normalization in borderline resectable (BR) and locally advanced (LA) PDAC has been associated with greater OS. The addition of cisplatin (C) to gemcitabine (G) and paclitaxel protein bound (A) has shown promising clinical data in a previously reported study in advanced PDAC (J Clin Oncol 2017;35:suppl 4S; abstract 341). We conducted a prospective, phase 2 clinical trial of patients with resectable, BR, and LA PDAC utilizing a regimen combining A + G + C + paricalcitol (P) with the primary endpoint of CA 19-9 normalization (NCT03138720). Methods: Eligibility criteria include patients with histologically confirmed resectable, BR, or LA PDAC, elevated CA 19-9, and a KPS ≥ 70% with normal end organ function. Doses are A 125 mg/m2, G 1000 mg/m2, C 25 mg/ m2, P at a fixed dose of 25 μg on days 1, 8 of a 21-day cycle (all treatment IV). Primary objective is to evaluate CA 19-9 normalization with the neoadjuvant chemotherapy. Secondary objectives are to assess R0 rate, pathologic complete response (pCR), safety and tolerability, radiologic response rate, and 2-year overall survival (OS) from date of study entry. Exploratory objectives include evaluating imaging biomarkers and vascular involvement by tumor in relation to therapy. Results: To date, 21 of the planned 24 patients have been enrolled: 11 male, 10 female; age range 49 to 85 yo. Patient classifications are 7 R; 7 BR; 7 LAPC. Most common drug-related grade (gr) 3-4 adverse events (AEs) are thrombocytopenia gr 3 40%, gr 4 33%, anemia gr 3 60%, and hypophosphatemia 13%. Of the 21, 16 are evaluable for maximum percent decrease in CA 19-9. CA 19-9 normalization occurred in 44% (7/16) who have completed at least 1 cycle of treatment. To date, 9 individuals went to surgery, with 8/9 achieving R0 (no pCR). Overall response rate in measurable patients is 26% (4/15 PR). Median OS and 2-year survival data are not yet matured. Conclusions: In patients with nonmetastatic PDAC, the use of A+G+C+P resulted in a CA 19-9 normalization rate in 44% of individuals. The study is ongoing and OS data are maturing. (Supported by grants from the HonorHealth Foundation and Marley Foundation.) Citation Format: Erkut Boraz