Phase I/II Trial of Neoadjuvant Oregovomab-based Chemoimmunotherapy Followed by Stereotactic Body Radiotherapy and Nelfinavir For Locally Advanced Pancreatic Adenocarcinoma

• Published in: American journal of clinical oncology Vol. 42; no. 10; p. 755
• Main Authors: Lin, Chi, Verma, Vivek, Lazenby, Audrey, Ly, Quan P, Berim, Lyudmyla D, Schwarz, James K, Madiyalakan, Madi, Nicodemus, Christopher F, Hollingsworth, Michael A, Meza, Jane L, Are, Chandrakanth, Padussis, James, Grem, Jean L
• Format: Journal Article
• Language: English
• Published: United States 01.10.2019
• Subjects: Adenocarcinoma - diagnostic imaging; Adenocarcinoma - mortality; Adenocarcinoma - pathology; Adenocarcinoma - therapy; Adult; Aged; Antibodies, Monoclonal, Murine-Derived - therapeutic use; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; CA-125 Antigen - blood; Camptothecin - adverse effects; Camptothecin - analogs & derivatives; Camptothecin - therapeutic use; Combined Modality Therapy; Disease-Free Survival; Female; Fluorouracil - adverse effects; Fluorouracil - therapeutic use; Follow-Up Studies; Humans; Kaplan-Meier Estimate; Leucovorin - adverse effects; Leucovorin - therapeutic use; Magnetic Resonance Imaging - methods; Male; Membrane Proteins - blood; Middle Aged; Nelfinavir - adverse effects; Nelfinavir - therapeutic use; Neoadjuvant Therapy - methods; Neoplasm Invasiveness - pathology; Organoplatinum Compounds - adverse effects; Organoplatinum Compounds - therapeutic use; Pancreatic Neoplasms - diagnostic imaging; Pancreatic Neoplasms - mortality; Pancreatic Neoplasms - pathology; Pancreatic Neoplasms - therapy; Pancreaticoduodenectomy - methods; Proportional Hazards Models; Radiosurgery - methods; Risk Assessment; Survival Analysis; Time Factors; Tomography, X-Ray Computed - methods; Treatment Outcome
• ISSN: 1537-453X
• DOI: 10.1097/COC.0000000000000599

Cancer antigen (CA)-125 influences progression, metastasis, and outcomes in pancreatic cancer. This phase I/II trial (NCT01959672) evaluated the safety, efficacy, and immunologic correlates of chemoimmunotherapy (CIT) with oregovomab (anti-CA-125), followed by stereotactic body radiotherapy (SBRT) with the radiosensitizer nelfinavir. Following imaging, pathologic confirmation, and staging laparoscopy, subjects received three 3-week cycles of CIT (gemcitabine/leucovorin/fluorouracil/oregovomab). Thereafter, nelfinavir was delivered (1250 mg bid) for 5 weeks, with SBRT (40 Gy/5 fractions) occurring during the third week of nelfinavir. Following another cycle of CIT, pancreaticoduodenectomy was performed if resectable. Three more cycles of CIT were then delivered (total 7 cycles). In subjects with high (≥10 U/mL) CA-125, oregovomab (2 mg) was administered for 7 total doses (3 pre-SBRT, 1 between SBRT and resection, and 3 postoperatively). The enzyme-linked immunospot assay evaluated the development of CA-125-specific CD8 T-lymphocytes. The trial was prematurely closed because gemcitabine/leucovorin/fluorouracil was replaced by FOLFIRINOX and gemcitabine/nab-paclitaxel as the standard of care. Median follow-up was 13 months. Of 11 enrolled patients, 10 had high CA-125; 1 patient suffered an unexpected cardiac-related death, so 9 subjects received oregovomab. Ten received SBRT and 4 underwent resection. Overall, 6/11 patients experienced any grade ≥3 event. The median survival and time to progression were 13 and 8.6 months, respectively. Five patients had samples available for immunospot testing, of whom 2 (40%) developed CA-125-specific CD8 T-lymphocytes. A combined pancreatic cancer multimodality approach using CIT and radiosensitized radiotherapy is feasible and safe; delivery of immunotherapy can lead to T-cell immunity. Re-evaluation with modern systemic paradigms is recommended.