Milella Michele, Orsi Giulia, di Marco Mariacristina, Salvatore Lisa, Procaccio Letizia, Noventa Silvia, Bozzarelli Silvia, Garajova Ingrid, Vasile Enrico, Giordano Guido, Macchini Marina, Cavaliere Alessandro, Gaule Marina, Bergamo Francesca, Chiaravalli Marta, Palloni Andrea, Carloni Riccardo, Bittoni Alessandro, Niger Monica, Rapposelli Ilario Giovanni, Rodriquenz Maria Grazia, Scartozzi Mario, Mosconi Stefania, Giommoni Elisa, Bernardini Ilaria, Paratore Chiara, Spallanzani Andrea, Bencardino Katia, Forti Laura, Tamburini Emiliano, Lonardi Sara, Scarpa Aldo, Cascinu Stefano, Tortora Giampaolo, Sperduti Isabella, Reni Michele
Department of Engineering for Innovation Medicine (DIMI), Specialty School in Medical Oncology and Section of Innovation Biomedicine-Oncology Area, Faculty of Medicine and Surgery, University of Verona, Verona, Italy.
Division of Oncology, Verona University and Hospital Trust (AOUI Verona), Verona, Italy.
Cancer Med. 2025 Feb;14(3):e70364. doi: 10.1002/cam4.70364.
Pancreatic cancer arising in the context of BRCA predisposition may benefit from poly(ADP-ribose) polymerase inhibitors. We analyzed real-world data on the impact of olaparib on survival in metastatic pancreatic cancer patients harboring germline BRCA mutations in Italy, where olaparib is not reimbursed for this indication.
Clinico/pathological data of pancreatic cancer patients with documented BRCA1-2 germline pathogenic variants who had received first-line chemotherapy for metastatic disease were collected from 23 Italian oncology departments and the impact of olaparib exposure on overall survival (OS) was analyzed.
Of 114, 53 BRCA-mutant pancreatic cancer patients had received olaparib for metastatic disease. OS was significantly longer in patients who were exposed to olaparib (hazard ratio [HR] 0.568, 95% confidence interval [CI] 0.351-0.918, log-rank p = 0.02) in any setting/line of treatment; similar results were obtained for patients who received olaparib as maintenance treatment (in any line of treatment), patients who had stage IV disease at diagnosis, and patients who did not experience progressive disease as their best response to first-line chemotherapy. Exposure to olaparib in the first-line maintenance setting after platinum-based chemotherapy, however, did not significantly impact survival. At multivariate analysis, CA19.9 levels at diagnosis and response to first-line chemotherapy were independently prognostic; however, when response to chemotherapy was excluded, any exposure to olaparib was a significant independent predictor of longer OS, together with CA19.9 levels.
The real-world data presented here support the use of olaparib for metastatic disease in germline BRCA-mutant pancreatic cancer patients, as it may significantly prolong survival.
在BRCA基因易感性背景下发生的胰腺癌可能从聚（ADP - 核糖）聚合酶抑制剂中获益。我们分析了在意大利奥拉帕利未被纳入该适应症医保报销范围的情况下，奥拉帕利对携带种系BRCA突变的转移性胰腺癌患者生存影响的真实世界数据。
从23个意大利肿瘤科室收集了有记录的BRCA1 - 2种系致病变异且接受过转移性疾病一线化疗的胰腺癌患者的临床/病理数据，并分析了奥拉帕利暴露对总生存期（OS）的影响。
在114例患者中，53例携带BRCA突变的胰腺癌患者接受了奥拉帕利治疗转移性疾病。在任何治疗背景/线别中，暴露于奥拉帕利的患者总生存期显著更长（风险比[HR] 0.568，95%置信区间[CI] 0.351 - 0.918，对数秩检验p = 0.02）；接受奥拉帕利作为维持治疗（在任何线别）的患者、诊断时为IV期疾病的患者以及对一线化疗最佳反应未出现疾病进展的患者也得到了类似结果。然而，在铂类化疗后的一线维持治疗中暴露于奥拉帕利对生存没有显著影响。在多变量分析中，诊断时的CA19.9水平和对一线化疗的反应是独立的预后因素；然而，当排除对化疗的反应后，任何奥拉帕利暴露与CA19.9水平一起都是总生存期延长的显著独立预测因素。
本文呈现的真实世界数据支持在携带种系BRCA突变的胰腺癌患者中使用奥拉帕利治疗转移性疾病，因为它可能显著延长生存期。
