Abstract
BACKGROUND: Immunotherapy has paved the way for new therapeutic opportunities in cancer but has failed to show any efficacy in Pancreatic Adenocarcinoma (PDAC), and its therapeutic role remains unclear. The objective of this study is to examine the impact of immunotherapy in combination with chemotherapy, RT, and chemoradiation on the overall survival (OS) of PDAC patients who received definitive surgery of the tumor using the National Cancer Database (NCDB). METHODS: Patients with PDAC who received definitive surgery of the pancreatic tumor and were diagnosed between 2004 and 2016 from the NCDB were identified. Cox proportional hazard analysis was used to assess the survival difference between patients who received chemotherapy plus immunotherapy and chemoradiation therapy plus immunotherapy and their counterparts who only receive these treatments without immunotherapy. The multivariable analysis was adjusted for age of diagnosis, race, sex, place of living, income, education, treatment facility type, insurance status, year of diagnosis, and treatment types such as chemotherapy and radiation therapy. RESULTS: In total, 63,154 PDAC patients who received definitive surgery of the tumor were included in the analysis. Among the 63,154 patients, 636 (1.01%) received immunotherapy. Among patients who received chemotherapy (21,355), and chemoradiation (21,875), 157/21,355 (0.74%) received chemotherapy plus immunotherapy, and 451/21,875 (2.06%) received chemoradiation plus immunotherapy. Patients who received chemoradiation plus immunotherapy had significantly improved median OS compared to patients who only received chemoradiation with an absolute median OS benefit of 5.7 [29.31 vs. 23.66, p < 0.0001] months. In the multivariable analysis, patients who received immunotherapy had significantly improved OS compared to patients who did not receive immunotherapy (HR: 0.900; CI: 0.814-0.995; P < 0.039). Patients who received chemoradiation plus immunotherapy had significantly improved OS compared to their counterparts who only received chemoradiation without immunotherapy (HR: 0.852 CI: 0.757-0.958; P < 0.008). CONCLUSIONS: In this study, the addition of immunotherapy to chemoradiation therapy was associated with significantly improved OS in PDAC patients who received definitive surgery. The study warrants further future clinical trials of immunotherapy in PDAC.