Effect of the addition of algenpantucel-L immunotherapy to standard adjuvant therapy on survival in patients with resected pancreas cancer.

Abstract

236 Background: Pancreatic cancer portends a poor prognosis with ∼4% long-term survival. Among the estimated 20% of patients who have resectable disease, the 1-/3-/5-year survival rates approximate only 70%/30%/18%, even with adjuvant therapy. Better treatment options are needed and addition of algenpantucel-L (HyperAcute-Pancreas) to standard adjuvant therapy is proposed to improve prospects for survival. Algenpantucel-L is composed of irradiated, live, allogeneic human pancreatic cancer cells expressing the enzyme α-1,3 galactosyl transferase (α-GT), which is the major barrier to xenotransplantation from lower mammals to humans (e.g., hyperacute rejection). Up to 2% of circulating human antibodies are directed against the α-GT epitope of algenpantucel-L and are the proposed mechanism of initiating the anti-tumor immune response. Methods: Open-label, single arm, multi-institutional phase II study (NLG0205) to evaluate algenpantucel-L + standard adjuvant therapy (RTOG-9704, JAMA, 2008: gemcitabine + 5-FU-XRT) for pancreatic cancer patients undergoing R0/R1 resection. Disease-free (DFS) and overall survival (OS) are the primary and secondary endpoints, respectively. Results: 73 patients (70 evaluable, 15 month median follow up) received gemcitabine + 5-FU-XRT + algenpantucel-L (mean 12 doses, range 1-14). Demographics and prognostic factors: median age 62 years, 47% female, 81.4% lymph node positive, median tumor size 3.2 cm (range 2-15 cm; 26% > 4cm) and 24% post-operative CA 19-9 > 90. Kaplan-Meier estimated survival rates at 12 and 24 months are 91% and 54%, respectively, comparing favorably to 63% and 32% expected based on the nomogram described by Brennan et al (Ann Surg, 2004). Likewise, the current median DFS of 16 months compares favorably to the 11 months observed in RTOG 9704. OS data continues to mature, with 74% still censored. Algenpantucel-L was well tolerated with no likely/directly attributable grade 3 SAEs. The most common adverse events were injection site pain and induration. Conclusions: Addition of algenpantucel-L to standard adjuvant therapy for resected pancreatic cancer may improve survival. A phase III study began patient enrollment in May 2010. [Table: see text]