POLO撞线：Olaparib在gBRCA突变的胰腺癌的一线维持治疗中显著降低疾病进展风险
Lynparza significantly delayed disease progression as 1st-line maintenance treatment in germline BRCA-mutated metastatic pancreatic cancer
（原文在最后）
之前该适应症研究被授予ODD
研究设计
所以其实不管是本推送还是官方标题都很拗口：应该是Olaparib在一线含铂化疗后不进展的胚系BRCA 突变的胰腺癌患者的维持治疗中（相比安慰剂）显著降低了疾病进展的风险，这样就舒畅很多了。
ClinicalTrial上临床登记：NCT02184195，Olaparib in gBRCA Mutated Pancreatic Cancer Whose Disease Has Not Progressed on First Line Platinum-Based Chemotherapy (POLO)
https://clinicaltrials.gov/ct2/show/NCT02184195
什么叫 significantly delayed？其实我也不知道有多 significantly，实在想知道的，自己对着SOLO1憧憬吧
根据之前的Report，POLO上半年出呆塔也是符合规划
BRCA突变与胰腺癌
单纯的BRCA突变只占3-5%，但是算上BRCAness也就是“DDR deficiency without BRCA mutations”涉及的其它基因PALB2, ATM, or CHK2突变 ，可以占到17%
https://letswinpc.org/promising-science/2018/07/05/potential-role-for-parp-inhibitors-pancreatic-cancer/
About 3 to 5 percent of pancreatic cancer patients also carry mutations in the BRCA genes. But there is also a concept called BRCAness, which involves mutations in other key BRCA-related genes such as PALB2, ATM, or CHK2. “When you look at other genes that have a BRCA-like phenotype, the target population for PARP in the pancreatic cancer setting could be as high as about 17 percent, thus expanding significantly the population of pancreatic cancer patients who could benefit from therapies like PARP inhibitors,” Pishvaian explains.
PARPi与胰腺癌
15年JCO上报导了一项Olaparib单药治疗gBRCA1/2突变的多类肿瘤的结果
其中胰腺癌患者亚组入组23人，中位年龄58岁，女性43.5%，ECOG 0、1和2分分别47。9%、39.1%和13.0%，全部携带胚系BRCA突变：只携带BRCA1突变21.7%、只携带BRCA2突变73.9%、BRCA1/2均突变的4.3%，先前接受治疗的中位数为2轮，全部在基线状态有可测量病灶。
ORR 21.7%(5/23，其中CR 1、PR 4)，SD≥8周占比35%(8/23，其中SD 5、未获确认的PR 3)
生存数据：PFS 4.6 mo、OS 9.8 mo
安全可耐受
做个简单的横向比较，延缓进展、延长OS——>PARPi治疗还是要尽量前移
https://cancerforum.org.au/wp-content/uploads/2016/03/11-FORUM_THE-CHANGING-LANDSCAPE-OF-SYSTEMIC-THERAPY-IN-ADVANCED-PANCREATIC-CANCER.pdf
友商方面：ASCO16上po了一项rucaparib治疗胰腺癌的数据，入组19 pts，68%患者先前接受过≥2L化疗，79%携带BRCA2突变。最终ORR 11%(1/19， 1 CR，1 PR)，另有1 pt又未确认的PR，所有产生缓解的患者都是先前只接受过1轮治疗。DCR 32%(6/19)，其中50%(3/6)先前只接受过1轮治疗。常见TRAE是恶心和贫血（各37%）,其中 ≥ 3级TRAE包括贫血(26%)、血小板减少(16%)和疲劳(11%)，目前CLOVIS并未开展胰腺癌的后续研究。
https://meetinglibrary.asco.org/record/125995/abstract
正文没干货
https://www.astrazeneca.com/media-centre/press-releases/2019/lynparza-significantly-delayed-disease-progression-as-1st-line-maintenance-treatment-in-germline-brca-mutated-metastatic-pancreatic-cancer-26022019.html
AstraZeneca and MSD Inc., Kenilworth, N.J., US (MSD: known as Merck & Co., Inc. inside the US and Canada) today announced positive results from the Phase III POLO trial.
Results from the trial showed a statistically-significant and clinically-meaningful improvement in progression-free survival (PFS) with Lynparza (olaparib) vs. placebo. The safety and tolerability profile of Lynparza was consistent with previous trials.
POLO is a randomised, double-blinded, placebo-controlled trial exploring the efficacy of Lynparza tablets as 1st-line maintenance monotherapy in patients with germline BRCA-mutated (gBRCAm) metastatic adenocarcinoma of the pancreas (pancreatic cancer) whose disease has not progressed on platinum-based chemotherapy.
José Baselga, Executive Vice President, Research and Development, Oncology, said: “This is the first positive Phase III trial of any PARP inhibitor in germline BRCA-mutated metastatic pancreatic cancer, a devastating disease with critical unmet need. The results of POLO provide further evidence of the clinical benefit of Lynparza across a variety of BRCA-mutated tumour types. We will discuss these results with global health authorities as soon as possible.”
Roy Baynes, Senior Vice President and Head of Global Clinical Development, Chief Medical Officer, MSD Research Laboratories, said: “Trials like POLO demonstrate the shared commitment of MSD and AstraZeneca to assess treatments for difficult-to-treat cancers. The clinically-meaningful results of this trial potentially support the value of testing for germline BRCA mutations in patients with metastatic pancreatic cancer.”
AstraZeneca and MSD plan to present the full data from the trial at a forthcoming medical meeting.