Immune Checkpoint Blockade in Combination with Stereotactic Body Radiotherapy in Patients with Metastatic Pancreatic Ductal Adenocarcinoma

• Published in: Clinical cancer research Vol. 26; no. 10; pp. 2318 - 2326
• Main Authors: Xie, Changqing, Duffy, Austin G, Brar, Gagandeep, Fioravanti, Suzanne, Mabry-Hrones, Donna, Walker, Melissa, Bonilla, Cecilia Monge, Wood, Bradford J, Citrin, Deborah E, Gil Ramirez, Elizabeth M, Escorcia, Freddy E, Redd, Bernadette, Hernandez, Jonathan M, Davis, Jeremy L, Gasmi, Billel, Kleiner, David, Steinberg, Seth M, Jones, Jennifer C, Greten, Tim F
• Format: Journal Article
• Language: English
• Published: United States 15-05-2020
• Subjects: Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal - administration & dosage; Antibodies, Monoclonal, Humanized - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - pharmacokinetics; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Carcinoma, Pancreatic Ductal - metabolism; Carcinoma, Pancreatic Ductal - pathology; Carcinoma, Pancreatic Ductal - therapy; Cohort Studies; Female; Follow-Up Studies; Humans; Immune Checkpoint Inhibitors - administration & dosage; Lymphatic Metastasis; Male; Middle Aged; Pancreatic Neoplasms - metabolism; Pancreatic Neoplasms - pathology; Pancreatic Neoplasms - therapy; Pilot Projects; Prognosis; Radiosurgery - methods; Survival Rate; Tissue Distribution
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-19-3624

The effectiveness of immune checkpoint inhibitors (ICI) is limited in pancreatic ductal adenocarcinoma (PDAC). We conducted a phase I study to evaluate the safety of ICI with stereotactic body radiation therapy (SBRT) in patients with metastatic PDAC.
Patients enrolled must have received at least one line of prior systemic chemotherapy for metastatic disease. Cohorts A1 and A2 received durvalumab every 2 weeks plus either 8 Gy in one fraction of SBRT on day 1 or 25 Gy in five fractions on day -3 to +1. Cohorts B1 and B2 received durvalumab plus tremelimumab every 4 weeks and either 8 Gy in one fraction of SBRT on day 1 or 25 Gy in five fractions on day -3 to +1. ICIs were continued until unacceptable toxicity or disease progression. The primary objective was the safety and feasibility of treatment. Objective response was assessed in lesions not subjected to SBRT.
Fifty-nine patients were enrolled and 39 were evaluable for efficacy. No dose-limiting toxicities were seen. The most common adverse event was lymphopenia. Two patients achieved a partial response (one confirmed and the other unconfirmed). The overall response rate was 5.1%. Median PFS and OS was 1.7 months [95% confidence intervals (CI), 0.8-2.0 months] and 3.3 months (95% CI, 1.2-6.6 months) in cohort A1; 2.5 months (95% CI, 0.1-3.7 months) and 9.0 months (95% CI, 0.5-18.4 months) in A2; 0.9 months (95% CI, 0.7-2.1 months) and 2.1 months (95% CI, 1.1-4.3 months) in B1; and 2.3 months (95% CI, 1.9-3.4 months) and 4.2 months (95% CI, 2.9-9.3 months) in B2.
The combination of ICI and SBRT has an acceptable safety profile and demonstrates a modest treatment benefit in patients with metastatic PDAC.