Platinum response characteristics of patients with pancreatic ductal adenocarcinoma and a germline BRCA1, BRCA2 or PALB2 mutation
Platinum response characteristics of patients with pancreatic ductal adenocarcinoma and a germline BRCA1, BRCA2 or PALB2 mutation
复制标题
DOI：
10.1038/s41416-019-0582-7
复制
发表时间：
2020-02-04
影响因子：
8.8
通讯作者：
Reiss, Kim A.
中科院分区：
文献类型：
--
作者：
Wattenberg, Max M.;Asch, Daniella;Reiss, Kim A.
背景：回顾性研究表明，对携带BRCA1、BRCA2或PALB2（突变阳性PDAC）种系突变的胰腺癌患者给予铂类化疗可提高生存率。然而，这种治疗的客观缓解率（ORR）和真实世界无进展生存期（rwPFS）仍然不明确。方法：26例接受铂基治疗的晚期突变阳性PDAC患者与52例接受铂基治疗的对照PDAC患者按年龄、种族和性别进行匹配。对治疗的反应由RECIST v1.1确定，通过盲法放射学回顾进行。测量结果包括ORR和rwPFS。结果：mut阳性患者的ORR为58%，对照组为21% （p = 0.0022）。在mut阳性患者中，铂治疗方案之间的ORR无显著差异（p = 0.814），而在对照患者中，唯一观察到的反应是对FOLFIRINOX。阳性患者的rwPFS为10.1 mo.，对照组为6.9 mo. （HR 0.43; 95% CI 0.25-0.74; 0.0068）。结论：mut1阳性PDAC对铂基化疗具有较高的ORR和较长的rwPFS。这些发现可能对新辅助治疗和未来临床试验设计具有重要意义，并强调了PDAC患者早期种系检测的重要性。
BACKGROUND: Retrospective studies suggest a survival benefit when platinum-based chemotherapy is administered to patients with pancreatic cancer harbouring a germline mutation in BRCA1, BRCA2 or PALB2 (mut-positive PDAC). However, the objective response rate (ORR) and real-world progression free survival (rwPFS) achieved with such treatment remain ill-defined.METHODS: Twenty-six patients with advanced-stage mut-positive PDAC who had been treated with platinum-based therapy were matched by age, race and sex to 52 platinum-treated control PDAC patients. Responses to therapy were determined by RECIST v1.1, performed by blinded radiology review. Measured outcomes included ORR and rwPFS.RESULTS: The ORR in mut-positive patients was 58% compared to 21% in the control group (p = 0.0022). There was no significant difference in ORR between platinum regimens in mut-positive patients (p = 0.814), whereas in control patients, the only observed responses were to FOLFIRINOX. rwPFS was 10.1 mo. for mut-positive patients and 6.9 mo. for controls (HR 0.43; 95% CI 0.25-0.74; 0.0068).CONCLUSION: Mut-positive PDAC has a high ORR and prolonged rwPFS to platinum-based chemotherapy. These findings may have implications particularly in the neoadjuvant setting, and for future clinical trial design, and highlight the importance of early germline testing in patients with PDAC.