Retrospective efficacy analysis of olaparib combined with bevacizumab in the treatment of advanced colorectal cancer

BACKGROUND Colorectal cancer(CRC)is a highly prevalent malignancy of the digestive tract worldwide,characterized by a significant morbidity and mortality rate and subtle initial symptoms.Diarrhea,local abdominal pain,and hematochezia occur with the development of cancer,while systemic symptoms such as anemia and weight loss occur in patients with advanced CRC.Without timely interventions,the disease can have fatal consequences within a short span.The current therapeutic options for colon cancer include olaparib and bevacizumab,which are widely utilized.This study intends to evaluate the clinical efficacy of olaparib combined with bevacizumab in the treatment of advanced CRC,hoping to provide insights into advanced CRC treatment.AIM To investigate the retrospective efficacy of olaparib combined with bevacizumab in the treatment of advanced CRC.METHODS A retrospective analysis was conducted on a cohort of 82 patients with advanced colon cancer who were admitted to the First Affiliated Hospital of the University of South China between January 2018 and October 2019.Among them,43 patients subjected to the classical FOLFOX chemotherapy regimen were selected as the control group,and 39 patients undergoing treatment with olaparib combined with bevacizumab were selected as the observation group.Subsequent to different treatment regimens,the short-term efficacy,time to progression(TTP),and incidence rate of adverse reactions between the two groups were compared.Changes in serum-related indicators[vascular endothelial growth factor(VEGF),matrix metalloprotein-9(MMP-9),cyclooxygenase-2(COX-2)]and tumor markers[human epididymis protein 4(HE4),carbohydrate antigen 125(CA125),carbohydrate antigen 199(CA199)]levels before and after treatment were compared between the two groups at the same time.RESULTS The objective response rate was discovered to be 82.05%,and the disease control rate was 97.44%in the observation group,which were significantly higher than the respective rates of 58.14%and 83.72%in the control group(P<0.05).The median TTP was 24 mo(95%CI:19.987-28.005)in the control group and 37 mo(95%CI:30.854-43.870)in the observation group.The TTP in the observation group was significantly better than that in the control group,and the difference held statistical significance(log-rank test value=5.009,P=0.025).Before treatment,no substantial difference was detected in serum VEGF,MMP-9,and COX-2 levels and tumor markers HE4,CA125,and CA199 levels between the two groups(P>0.05).Following treatment with different regimens,the above indicators in the two groups were remarkably promoted(P<0.05),VEGF,MMP-9,and COX-2 in the observation group were lower than those in the control group(P<0.05),and HE4,CA125,and CA199 levels were also lower than those in the control group(P<0.05).Visà-vis the control group,the total incidence of gastrointestinal reactions,thrombosis,bone marrow suppression,liver and kidney function injury,and other adverse reactions in the observation group was notably lowered,with the difference considered statistically significant(P<0.05).CONCLUSION Olaparib combined with bevacizumab in the treatment of advanced CRC demonstrates a strong clinical effect of delaying disease progression and reducing the serum levels of VEGF,MMP-9,COX-2 and tumor markers HE4,CA125 and CA199.Moreover,given its fewer adverse reactions,it can be regarded as a safe and reliable treatment option.

PARP抑制剂olaparib对急性髓系白血病细胞HL-60抑制作用研究

目的研究PARP抑制剂olaparib对人急性髓系白血病细胞株HL-60细胞的抑制作用。方法对数生长期HL-60细胞经不同浓度(0、1.25、2.5、5、10μmol/L)olaparib作用不同时间后,CCK-8法检测olaparib对HL-60细胞的增殖抑制作用;Annexin-V/PI双标法检测HL-60细胞凋亡水平,Western blot检测HL-60细胞内相关信号蛋白(PARP-1、Caspase-3)表达变化。结果与对照组相比,经不同浓度(1.25、2.5、5、10μmol/L)olaparib作用48 h后的HL-60细胞出现增殖抑制,并且随着作用时间的延长,抑制率逐渐增加;同时发现olaparib诱导HL-60细胞发生凋亡,并显示出剂量依赖效应;Western blot结果显示,olaparib处理后的HL-60细胞内PARP活性受到抑制,Caspase-3活化。结论PARP抑制剂olaparib对HL-60细胞不仅具有增殖抑制作用,同时可通过激活Caspase-3,抑制PARP活性,诱导HL-60细胞凋亡。

Olaparib对HL-60细胞NKG2D配体表达的调节作用及相关机制研究

目的:研究Olaparib对人急性髓系白血病细胞株HL-60细胞表面NKG2D配体表达的调节作用,并初步探索其内在调控机制。方法:对数生长期的HL-60细胞经不同浓度Olaparib(1.25、2.5、5、10μmol/L)作用24、48 h后,采用流式细胞术检测细胞表面NKG2D配体表达情况;Western blot检测HL-60细胞内ERK蛋白表达变化情况;CFSE/PI法检测NK细胞对HL-60细胞的杀伤作用。结果:10μmol/L Olaparib作用24和48 h均可上调HL-60细胞表面NKG2D配体的表达,5μmol/L Olaparib作用48 h可诱导ULBP-2、ULBP-3表达上调;Western blot检测结果显示,Olaparib处理后的HL-60细胞内ERK磷酸化水平增强。Olaparib可增强NK细胞对HL-60细胞的杀伤作用,但ERK抑制剂可下调NK细胞对HL-60细胞的杀伤作用。结论:Olaparib可上调HL-60细胞表面NKG2D配体表达,增强NK细胞对其的杀伤作用,其机制可能与Olaparib促进ERK磷酸化表达有关。

The New England Journal of Medicine:Olaparib,前列腺癌精准治疗里程碑

一项重要的新的临床试验证实,最初研发用于治疗罹患遗传性癌症妇女的一种开拓性药物,也可以让晚期前列腺癌患者受益。这一试验是前列腺癌治疗的一个里程碑,它第一次证实了“精准医疗”——采取与患者肿瘤特殊遗传特征相匹配的疗法对前列腺癌有好处。试验结果最近由英国癌症研究院和皇家Marsden NHS信托基金会的研究人员领导的一个国际团队发表在《新英格兰医学杂志》（MATEO J,CARREIRA S, SANDHU S, et al. the New Eng J Med, 2015,373： 1697-1708）上。

Response of BRCA1-mutated gallbladder cancer to olaparib: A case report

gallbladder cancer(gbc), although considered as a relatively rare malignancy, is the most common neoplasm of the biliary tract system. the late diagnosis and abysmal prognosis present challenges to treatment. the overall 5-year survival rate for metastatic gbc patients is extremely low. BRC A1 and BRCA2 are the breast cancer susceptibility genes and their mutation carriers are at a high risk for cancer development, both in men and women. Olaparib, an oral poly ADP-ribose polymerase inhibitor, has been approved by the Food and Drug Administration and the European commission for the treatment of ovarian cancer with any BRCA1/2 mutations. the first case of BRCA1-mutated gbc patient who responded to olaparib treatment is reported here.

Impact of Olaparib for Maintenance Monotherapy on Survival in Breast and Ovarian Cancer: A Systematic Review and Pooled Analysis of Published Trials

Purpose: To assess the efficacy and safety of Olaparib, a PARP inhibitor on progression-free survival (PFS), objective response rate (ORR) and overall survival (OS) in patients with breast and ovarian cancer. Methods: Research data from clinical trials through PubMed, Science Citation Index, Elsevier Science Direct and Cochrane Library of all published studies exploring the PFS, ORR or OS of Olaparib for maintenance monotherapy on survival in breast and ovarian cancer were analysed. Pooled estimates of the ORR, weighted medians of PFS and OS from all Olaparib were calculated. Assessment of quality and level of evidence was assigned by Cochrane guidelines and guidelines of Oxford Centre for Evidence-Based Medicine. Results: Data of 893 patients (731 olaparib;162 control) from 6 trials, 2 randomised controlled trials and 4 non-randomised trials, were included. The overall median weighted PFS and OS in patients treated with Olaparib were 5.9 and 19.1 months, respectively. The pooled ORR was 25%. Olaparib showed a greater effect on PFS in patients with both wild-type BRCA and BRCA mutant gene. The most common toxicity were nausea and vomiting. Conclusions: Olaparib as maintenance monotherapy for breast and ovarian cancer is associated with promising outcomes including increased response rate and improved PFS. Its potential in clinical application is needed for further investigation in phase III trials.

Pancreatic mucinous cystadenocarcinoma in a patient harbouring BRCA1 germline mutation effectively treated with olaparib: A case report

BACKGROUND Pancreatic mucinous cystadenocarcinoma(MCAC)is a rare malignancy with a poor prognosis when it presents metastases at diagnosis.Due to its very low incidence,there are no clear recommendations for the treatment of advanced disease.Olaparib(an oral PARP inhibitor)has been approved for the maintenance treatment of patients with metastatic pancreatic adenocarcinoma harbouring germline BRCA1/2 mutations.Herein,we report the first case of a germline BRCA1 mutated unresectable MCAC which was effectively treated with olaparib.CASE SUMMARY A 41-year-old woman,without personal or family history of cancer,was diagnosed with ovarian and peritoneal metastases of MCAC.She underwent 12 cycles of gemcitabine plus oxaliplatin(GEMOX)obtaining a partial response and allowing radical surgery.One year later,local recurrence was documented,and other 12 cycles of GEMOX were administered obtaining a complete response.Seven years later,another local recurrence,not amenable to surgical resection,was diagnosed.She started FOLFIRINOX(oxaliplatin,irinotecan,leucovorin and fluorouracil),obtaining a partial response after 8 cycles.Given the excellent response to platinum-based chemotherapy,BRCA testing was performed,and a BRCA1 germline mutation was detected.She was switched to maintenance olaparib due to chemotherapy-related toxicities and achieved an almost complete metabolic response,with a reduction in the diameter of the lesion,after three months of therapy.CONCLUSION The current case suggests the beneficial effect of olaparib in BRCA mutated MCAC.However,further studies are required.

Circulating tumor DNA genomic profiling reveals the complicated olaparib-resistance mechanism in prostate cancer salvage therapy: A case report

BACKGROUND The poly(ADP-ribose)polymerase(PARP)inhibitor olaparib has displayed superior clinical effect in metastatic castration-resistant prostate cancer(mCRPC)patients with the homologous recombination repair(HRR)genes mutations.However,when a patient’s tumor tissue volume is insufficient for genomic profiling of HRR gene mutations,circulating tumor DNA(ctDNA)may be useful in helping to determine and monitor the efficacy of olaparib,as well as in abiraterone-combination treatment,and for understanding any resistance mechanism related to such mutations.CASE SUMMARY A 61-year-old man who was diagnosed with metastatic prostate adenocarcinoma was initially hormone sensitivity,showing high Gleason score(5+5=10)and absolute positive rate(14/14 biopsied specimens).Following failure of several standard therapies,the patient progressed to mCRPC.Surprisingly,the patient showed good response to olaparib-abiraterone-prednisone combination treatment(an androgen-deprivation therapy,provided as the‘final choice’in China).Serum total prostate-specific antigen(TPSA)level reduced and symptoms remitted for 4 months.However,thereafter,serum TPSA levels began slowly increasing,indicating development of olaparib resistance.Subsequent comprehensive genomic profiling of ctDNA, screening 508 cancer-related genes by next-generation sequencing,identified 10 somatic variants as well as 3 copy number alterations. Two identified reversemissense mutations in partner and localizer of BRCA2 (PALB2) may have recovered the readingframe, restoring function of the primary germline PALB2 mutation and causing resistance to thePARP inhibitor olaparib.CONCLUSIONReverse mutations in PALB2, discovered via genomic profiling of ctDNA, may represent apotential resistance mechanism against olaparib in mCRPC.

美国FDA批准Lynparza(olaparib)用于治疗晚期卵巢癌

美国FDA于2014年12月19日批准Lynparza（olaparib）用于治疗因BRCA基因（gB RCAm）突变引起的晚期卵巢癌。FDA同时批准了一种对BRCA基因突变进行检测的仪器,名为BRACAnalysis CDx。 BRCA基因可以修复受损的DNA,抑制肿瘤细胞的生长。发生BRCA基因突变的女性更容易患卵巢癌。据估计，约10％～15％的卵巢癌患者与这种遗传性的BRCA基因突变有关。经BRACAnalysis CDx检测确认有BRCA基因突变的卵巢癌患者可接受Lynparza治疗。

阿斯利康PARP抑制剂Lynparza(olaparib)获得欧盟委员会批准

近日,阿斯利康宣布其PARP抑制剂Lynparza(olaparib)获得欧盟委员会批准作为一线维持疗法,用于BRCA突变的晚期卵巢癌患者。Lynparza是全球上市的首个PARP抑制剂,2014年12月首次获得美国FDA批准用于携带有害或疑似有害种系BRCA突变(gBRCAm)的晚期卵巢癌患者。2018年12月获得美国FDA的批准作为一线维持治疗BRCAm晚期卵巢癌。

Enzalutamide and olaparib synergistically suppress castration-resistant prostate cancer progression by promoting apoptosis through inhibiting nonhomologous end joining pathway

Recent studies revealed the relationship among homologous recombination repair(HRR),androgen receptor(AR),and poly(adenosine diphosphate-ribose)polymerase(PARP);however,the synergy between anti-androgen enzalutamide(ENZ)and PARP inhibitor olaparib(OLA)remains unclear.Here,we showed that the synergistic effect of ENZ and OLA significantly reduced proliferation and induced apoptosis in AR-positive prostate cancer cell lines.Next-generation sequencing followed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses revealed the significant effects of ENZ plus OLA on nonhomologous end joining(NHEJ)and apoptosis pathways.ENZ combined with OLA synergistically inhibited the NHEJ pathway by repressing DNA-dependent protein kinase catalytic subunit(DNA-PKcs)and X-ray repair cross complementing 4(XRCC4).Moreover,our data showed that ENZ could enhance the response of prostate cancer cells to the combination therapy by reversing the anti-apoptotic effect of OLA through the downregulation of anti-apoptotic gene insulin-like growth factor 1 receptor(IGF1R)and the upregulation of pro-apoptotic gene death-associated protein kinase 1(DAPK1).Collectively,our results suggested that ENZ combined with OLA can promote prostate cancer cell apoptosis by multiple pathways other than inducing HRR defects,providing evidence for the combined use of ENZ and OLA in prostate cancer regardless of HRR gene mutation status.

PARP抑制剂olaparib

olaparib是一种聚腺苷二磷酸核糖聚合酶(PARP)抑制剂,能选择性地作用于BRCA突变阳性的肿瘤细胞,利用"协同致死性"机制使肿瘤细胞因双链DNA损伤无法修复而死亡。2014年12月,欧盟和美国先后批准其上市,用于治疗BRCA基因突变阳性的晚期卵巢癌患者,疗效显著,不良反应少,患者短期耐受性良好,具有广泛的应用前景。现对其药理作用、药动学、药物相互作用、临床试验以及不良反应等方面进行综述。

奥拉帕尼诱导乳腺癌MCF-7细胞衰老作用及其机制

目的 研究奥拉帕尼(olaparib)诱导乳腺癌MCF-7细胞衰老作用的表现及其相关分子水平作用机制。方法 利用实时细胞分析(real-time cell analysis, RTCA)技术实时动态检测抗增殖和抗迁移活性;应用衰老相关β-半乳糖苷酶(senescence-associated β-galactosidase, SA-β-gal)染色法观察诱导细胞衰老活性;通过qPCR分析奥拉帕尼对衰老相关基因p16、p21、C/EBP同源蛋白(C/EBP homologous protein, CHOP)、白细胞介素(interleukin, IL)-6、IL-8、纤溶酶原激活物抑制剂-1(plasminogen activator inhibitor 1,PAI-1)、磷酸酶和张力蛋白同源物(phosphatase and tensin homolog deleted on chromosome 10,PTEN)、p27、视网膜母细胞瘤基因(retinoblastoma gene, RB1)、Ki67和E2F1表达的影响;根据Western Blot分析奥拉帕尼对衰老相关蛋白p21、γH2AX、胰岛素样生长因子结合蛋白3(insulin-like growth factor binding protein 3,IGFBP3)、cyclin D1、pRB和Ki67表达的影响。结果 奥拉帕尼能够抑制乳腺癌MCF-7细胞增殖、迁移并诱导MCF-7细胞的衰老;奥拉帕尼作用96 h的MCF-7细胞中p16、p21、p27、CHOP、IL-6、IL-8、PAI-1、PTEN和RB1的基因表达水平显著上调(P<0.01),Ki67和E2F1的基因表达水平显著下调(P<0.01);MCF-7细胞中p21、γH2AX和IGFBP3蛋白的表达水平显著升高(P<0.01,P<0.01,P<0.05),cyclin D1、pRB和Ki67蛋白的表达水平显著降低(P<0.05,P<0.01,P<0.05)。结论 奥拉帕尼能够通过抗增殖、迁移和诱导细胞衰老产生抗乳腺癌MCF-7细胞作用。

奥拉帕利联合贝伐珠单抗方案对卵巢癌患者近期疗效及血清P-selectin、sICAM-1水平的影响

目的探讨奥拉帕利与贝伐珠单抗方案联合治疗对卵巢癌患者近期疗效及肿瘤标志物、T淋巴细胞、血清P-选择素(P-selectin)、可溶性细胞间粘附分子-1(sICAM-1)的影响。方法以2019年1月至2021年5月安阳市肿瘤医院收治的87例卵巢癌患者为研究对象,依据不同治疗方案分为参照组(43例)、研究组(44例)。参照组采用贝伐珠单抗治疗,研究组在参照组基础上增加奥拉帕利治疗。比较两组疾病控制率(DCR)、总缓解率(ORR)、毒副反应发生情况,比较治疗前、治疗30 d后血管内皮生长因子(VEGF)、糖类抗原(CA199、CA125)、癌胚抗原(CEA)、T淋巴细胞(CD4^(+)、CD8^(+)、CD3^(+)、CD4^(+)/CD8^(+))、P-selectin及sICAM-1水平。结果治疗后研究组ORR为70.45%(31/44),高于参照组的48.84%(21/43)(P<0.05);治疗后两组CEA、CA199、VEGF、sICAM-1、P-selectin及CA125水平均明显下降,其中研究组下降幅度更为显著(P<0.05);与治疗前比较,两组CD8^(+)水平均升高,CD4^(+)、CD3^(+)、CD4^(+)/CD8^(+)水平均降低(P<0.05);两组治疗后CD8^(+)、CD4^(+)、CD3^(+)、CD4^(+)/CD8^(+)比较,差异无统计学意义(P>0.05);两组肝肾损伤、血小板减少、胃肠道反应及黏膜出血等毒副反应比较,差异无统计学意义(P>0.05)。结论奥拉帕利与贝伐利珠单抗联合治疗卵巢癌疗效确切,可抑制新生血管生成,阻止肿瘤细胞扩散转移,降低肿瘤标志物水平,且对机体免疫功能影响较小。

临床药师参与1例前列腺癌患者应用奥拉帕利致间质性肺炎伴发热的治疗实践

目的:为发生奥拉帕利致间质性肺炎伴发热的前列腺癌患者用药监护提供参考。方法:对1例口服奥拉帕利片后出现间质性肺炎患者的诊疗过程进行分析,临床药师结合临床药学专业知识,从患者出现发热的原因、间质性肺炎的治疗措施等方面进行分析,提出抗肿瘤治疗调整方案,并实施全程药学监护。结果:患者出现间质性肺炎后应及时停药,并根据不良反应严重程度调整后续治疗剂量,临床药师参与诊疗过程后患者间质性肺炎症状改善明显。结论:奥拉帕利引起的间质性肺炎较少见,临床应注意用药监护、及时调整用药方案并进行对症治疗,同时还需注意药物相互作用对奥拉帕利血药浓度的影响。

Synthesis of Olaparib Derivatives and Their Antitumor Activities

A series of Olaparib derivatives was synthesized, and their structures were confirmed by 1H NMR, MS and elemental analysis. Their antitumor activities on breast cancer susceptbility gene 1/2（BRCAl/2）-deficient cancer cell lines including HCC1937, Capan-1 and MDA-MB-436 were evaluated. The antitumor activity of compound Olaparib-1 was better than the positive control Olaparib in BRCAl-deficient cell line HCC1937.

奥拉帕利在肿瘤专科医院卵巢癌患者中的合理性和安全性研究

目的分析奥拉帕利在卵巢癌患者中使用的合理性和安全性。方法从我院HIS系统中抽取2020年7月-2021年6月确诊为卵巢癌且使用奥拉帕利治疗的全部病历,按照入选和排除标准选取病例,共计43例,统计分析其用药合理性以及安全性。结果9例(20.93%)患者存在用药不合理现象,表现为给药频次不适宜、剂量调整不适宜、未及时停药。36例(83.72%)患者出现贫血、中性粒细胞降低、血小板降低、恶心呕吐、肝肾功能受损等不良反应,其中3~4级不良反应发生率为41.86%(18/43),均表现为血液学毒性,严重贫血是最常见的3级以上不良反应。结论临床上存在口服奥拉帕利不合理使用情况,不良反应以贫血最为严重和常见,用药期间需要进行血常规和肝肾功能监测。

奥拉帕利辅助治疗对乳腺癌非保乳手术术后病理阳性患者预后、腋窝局部复发和远处复发的影响

目的探究奥拉帕利辅助治疗对乳腺癌非保乳手术术后病理阳性患者预后,腋窝局部复发和远处复发的影响。方法本研究为回顾性分析,选择2012年3月至2017年6月徐州市中心医院收治的60例乳腺癌非保乳手术治疗患者为研究对象,按照随机数字表法分为观察组(n=30)和对照组(n=30)。对照组开展多西紫杉醇、顺铂联合治疗,观察组在对照组治疗的基础上,予以奥拉帕利辅助治疗。比较肿瘤标志物[癌胚抗原(CEA)、糖链抗原(CA)-199和CA242]水平、机体免疫功能、细胞凋亡因子[B淋巴细胞瘤-2(Bcl-2)、可溶性细胞凋亡因子(sFas)、Bcl-2结合抗凋零基因-1(Bag-1)]、复发情况、不良反应。结果治疗后,两组CEA、CA199、CA242水平均较治疗前降低,且观察组分别为(16.56±2.36)μg/L、(49.96±6.25)U/mL、(98.56±10.25)U/mL,均低于对照组[(20.25±2.54)μg/L、(58.12±6.92)U/mL、(112.25±11.66)U/mL],差异均有统计学意义(P<0.05)。治疗后,两组CD3^(+)、CD4^(+)、CD4^(+)/CD8^(+)水平均较治疗前升高,CD8^(+)均较治疗前降低,且观察组CD3^(+)、CD4^(+)、CD4^(+)/CD8^(+)分别为(55.69±5.05)%、(56.58±5.16)%、1.96±0.31,均高于对照组[(50.95±5.11)%、(50.25±5.89)%、1.64±0.24],CD8^(+)为(28.89±2.65)%,低于对照组[(30.65±2.12)%],差异均有统计学意义(P<0.05)。治疗后,两组Bcl-2、sFas、Bag-1水平均较治疗前降低,Bax水平均较治疗前升高,且观察组Bcl-2、sFas、Bag-1水平为(0.85±0.13)ng/mL、(13.52±1.82)ng/mL、(10.25±1.12)μg/mL,均低于对照组[(1.39±0.22)ng/mL、(16.98±1.58)ng/mL、(15.62±2.35)μg/mL],Bax水平为(3.82±0.52)ng/mL,高于对照组[(3.29±0.50)ng/mL],差异均有统计学意义(P<0.05)。观察组局部复发率、远处复发率分别为0、13.33%,均低于对照组(11.76%、26.67%);观察组5年内生存率为96.67%,高于对照组(73.33%),差异均有统计学意义(P<0.05)。观察组不良反应总发生率为23.33%,对照组不良反应总发生率为16.67%,观察组与对照组比较,差异无统计学意义(P>0.05)。结论奥拉帕利辅助治疗可明显降低机体肿瘤标志物水平,提升细胞免疫功能,从而促使肿瘤细胞凋亡,降低疾病复发率,且安全性较高。

奥拉帕利辅助治疗BRCA1/2突变HER2阴性乳腺癌有效性与安全性的Meta分析

目的系统评价奥拉帕利辅助治疗乳腺癌易感基因(BRCA)1/2突变人表皮生长因子受体2(HER2)阴性乳腺癌的有效性和安全性,为临床治疗提供循证参考。方法计算机检索中国知网、维普、万方、PubMed、ScienceDirect、the Cochrane Library和Embase数据库,收集奥拉帕利辅助治疗(试验组)对比其他药物辅助治疗(对照组)的随机对照试验。筛选文献、提取数据后,采用RevMan 5.4软件进行Meta分析、发表偏倚分析和敏感性分析。结果共纳入5项随机对照试验,共计2633例患者,其中试验组1459例,对照组1174例。Meta分析结显示,在有效性方面,与对照组相比,试验组患者的总生存期[HR=1.02,95%CI(1.01,1.03),P=0.0008]和无进展生存期[HR=1.78,95%CI(1.46,2.17),P<0.00001]显著延长。在安全性方面,与对照组相比,试验组患者的任何级别不良反应发生率更高[RR=1.41,95%CI(1.12,1.78),P=0.004],而两组患者的3级以上不良反应发生率比较差异无统计学意义[RR=1.75,95%CI(0.82,3.74),P=0.15]。发表偏倚结果显示,本研究存在发表偏倚的可能性较小。敏感性分析结果显示,本研究所得结果稳健。结论与非奥拉帕利辅助治疗的患者相比,奥拉帕利辅助治疗BRCA1/2突变HER2阴性乳腺癌可延长患者的总生存期和无进展生存期,但不良反应发生风险相对较高。

奥拉帕利多晶型及晶型转化研究

奥拉帕利是全球首个上市的聚腺苷二磷酸-核糖聚合酶抑制剂。研究了奥拉帕利形成异质同晶溶剂化物的现象的机理,并进一步通过四氢呋喃溶剂化物单晶解析了奥拉帕利异质同晶溶剂化物的类型为独立位点型;研究了奥拉帕尼无水晶型A/L热力学稳定关系,分析了溶剂介导下稳定晶型向介稳晶型异常转变的可能原因;同时考察了温度和水体积比对无水晶型A与水合物晶型H相变过程的影响。