Real-world impact of olaparib use in advanced pancreatic cancer (PC) patients (pts) harboring germline BRCA1/2 (gBRCA) mutations

gBRCA mutations are found in approximately 8% of Italian PC pts screened within 3 months from diagnosis. gBRCA PC pts display enhanced sensitivity to platinum-based chemotherapy (CHT) and PARP inhibitors, such as olaparib. In metastatic gBRCA PC pts, maintenance olaparib after platinum-based CHT doubled PFS and resulted in twice as many long-term (3-yr) survivors (34% versus 18%) in the randomized POLO trial. However, despite guideline recommendations, olaparib is currently not reimbursed in Italy in metastatic gBRCA PC pts, based on the absence of significant differences in median OS. We analyzed the impact of exposure to olaparib on OS from the start of I-line treatment in a cohort of 114 Italian gBRCA PC pts, whose clinical characteristics and outcomes in response to first (10.1016/j.esmoop.2021.100238) and subsequent (manuscript submitted) chemotherapy lines have been previously reported. In the entire cohort, OS from the start of I-line treatment for metastatic disease was significantly (p=0.02) longer in pts who had been exposed to olaparib in any treatment line (n=53; Table); similar results were obtained analyzing only pts who had received olaparib in its current indication (n=43). Since previous surgery and response to I-line chemotherapy were strong independent predictors of OS at multivariate analysis, we analyzed pts who were diagnosed with stage IV (M+, n=87) disease and pts who did not experience PD as best response to I-line CHT (no PD, n=94), separately. A statistically significant difference in OS favoring gBRCA PC pts who were exposed to olaparib in any line of treatment was observed in the M+ cohort (p=0.0025), in the no PD cohort (p=0.049), and in the M+/no PD cohort (n=73, p=0.019).Table: 1307PAny olaparibmOS (mos; 95% CI)p valueEntire cohort (n=114)No (n=61)16 (12-20)0.02Yes (n=53)34 (24-44)M+ cohort (n=87)No (n=47)14 (11-18)0.0025Yes (n=40)34 (25-43No PD cohort (n=93)No (n=43)17 (8-25)0.049Yes (n=50)34 (24-43)No PD/M+ cohort (n=73)No (n=35)16 (12-20)0.019Yes (n=38)34 (24-44) Open table in a new tab In gBRCA PC pts, exposure to olaparib in any line of treatment in a real-world setting significantly impacts on OS, further supporting its use in the current indication (I-line maintenance after platinum-based CHT).