Background: Limited data are available regarding the anticancer activity of PARP inhibitors (PARPis) in pancreatic cancer with mutations in HRR genes other thanBRCAandPALB2. Methods: We retrospectively reviewed the clinical characteristics and outcomes of 48 patients with advanced pancreatic cancer harboring pathogenic germline and/or somatic HRR mutations who were treated with PARPis. Results: Thirty patients had germline (g)HRR mutations only, twelve had somatic (s)HRR mutations only, and six had concomitant gHRR and sHRR mutations. The objective response rate (ORR) was 22%. The median progression-free survival (mPFS) and overall survival (mOS) were 6.9 and 11.5 months, respectively. Five patients received olaparib in the front-line setting due to borderline performance status. Their ORR was 20%, and their mPFS and mOS were both 11.3 months. The ORR was higher in patients withBRCAorPALB2mutations (germline or somatic) than in those with non-BRCA/PALB2mutations. Patients with somatic non-BRCA/PALB2variants had a shorter mPFS. Patients with concomitant gHRR/sHRR mutations or gHRR mutations alone had a significantly longer mPFS than those with sHRR mutations only. Conclusions: PARP inhibitors may be considered for patients with advanced pancreatic cancer harboring pathogenic alterations ofBRCAwho cannot tolerate standard chemotherapy. Maintenance PARPis can be considered in selected patients with non-BRCA/non-PALB2HRR mutations.
背景：关于PARP抑制剂（PARPis）在携带除BRCA和PALB2外同源重组修复（HRR）基因突变的胰腺癌中的抗癌活性，现有数据有限。方法：我们回顾性分析了48例携带致病性胚系和/或体细胞HRR突变的晚期胰腺癌患者接受PARPis治疗的临床特征及结局。结果：30例患者仅携带胚系（g）HRR突变，12例仅携带体细胞（s）HRR突变，6例同时存在gHRR和sHRR突变。客观缓解率（ORR）为22%。中位无进展生存期（mPFS）和中位总生存期（mOS）分别为6.9个月和11.5个月。5例患者因体能状态处于临界水平而在一线接受奥拉帕利治疗，其ORR为20%，mPFS和mOS均为11.3个月。携带BRCA或PALB2突变（胚系或体细胞）患者的ORR高于携带非BRCA/PALB2突变的患者。携带体细胞非BRCA/PALB2变异患者的mPFS较短。同时存在gHRR/sHRR突变或仅存在gHRR突变的患者，其mPFS显著长于仅存在sHRR突变的患者。结论：对于携带BRCA致病性变异且无法耐受标准化疗的晚期胰腺癌患者，可考虑使用PARP抑制剂。对于部分经过筛选的非BRCA/非PALB2 HRR突变患者，可考虑采用PARPis进行维持治疗。
肿瘤(癌症)患者之家