2015年ASCO年會將于5月29日—6月2日在美國芝加哥召開。5月31日上午的消化系統(tǒng)（非結(jié)直腸）腫瘤口頭報(bào)告專場，會發(fā)表一項(xiàng)在IV期，未經(jīng)治療的胰腺癌高-HA腫瘤患者中，將PEGPH20加入白蛋白結(jié)合型紫杉醇/吉西他濱的II期研究結(jié)果。整理如下：

    胰腺癌（PDA）較差的預(yù)后部分與腫瘤間質(zhì)限制性化療灌注有關(guān)。PDAs透明質(zhì)酸（HA）高水平表達(dá)，有助于升高組織間隙壓力。聚乙二醇化重組人透明質(zhì)酸酶，PEGPH20,消耗了腫瘤中的HA.在一項(xiàng)PEGPH20+吉西他濱（Gem）的Ib期研究中，與HA低的腫瘤患者（pts）相比較，HA高的腫瘤患者會有改善的ORR,PFS和OS.

    研究方法：

    這是一項(xiàng)正在進(jìn)行的II期，開放標(biāo)簽，隨機(jī)研究，在之前未經(jīng)治療的IV期胰腺癌患者中，將PEGPH20+白蛋白結(jié)合紫杉醇（Nab）+Gem（PAG）和Nab+Gem進(jìn)行比較?；颊呓邮躊EGPH20 3?g/kg,每周兩次（Cycle 1），然后每周一次（Cycle 2+），聯(lián)合標(biāo)準(zhǔn)劑量的AG.HA狀態(tài)進(jìn)行回顧性檢查。主要終點(diǎn)是PFS,次要終點(diǎn)包括：ORR,OS和安全性。由于暫時(shí)的臨床擱置，ORR是來自2014年4月的數(shù)據(jù)；PFS是一直到2014年12月的數(shù)據(jù)。

    研究結(jié)果：

    146例患者入組，135例患者接受至少一種研究藥物劑量。平均年齡是65.1歲（范圍29——83歲），93%出現(xiàn)≥80的KPS.最常見與研究藥物（PAG vs AG）相關(guān)的不良事件是：疲勞（68% vs 69%），惡心（55% vs 44%），貧血（42% vs 53%），外周水腫（58% vs 31%），以及肌肉痙攣（55% vs 2%）。血栓栓塞（TE）事件呈現(xiàn)不平衡（42% vs 25%），這些患者中至少發(fā)生一例TE事件。總的RR和PFS如下表所示。
 

    結(jié)論：

    PEGPH20+Nab/Gem在晚期胰腺癌中一般耐受性良好。HA高的腫瘤患者接受PAG,與接受AG治療相比較，會有較大的ORR和較長的PFS.總生存期將在會議期間提交。臨床試驗(yàn)信息：NCT01839487.

    閱讀原文摘要

    High response rate and PFS with PEGPH20 added to nab-paclitaxel/gemcitabine in stage IV previously untreated pancreatic cancer patients with high-HA tumors: Interim results of a randomized phase II study.（Abstract 4006）Authors:Sunil R. Hingorani, William Proctor Harris,et al.

    Session Type:Oral Abstract Session

    Background: Poor outcomes in pancreatic cancer （PDA） are associated in part with tumor stroma limiting chemotherapy perfusion. PDAs express high levels of hyaluronan （HA）， which contributes to elevated interstitial pressures. PEGylated recombinant human hyaluronidase, PEGPH20, depletes HA in tumors. In a Phase Ib study of PEGPH20 with Gemcitabine （Gem）， patients （pts） whose tumors were HAhigh had improved ORR, PFS and OS compared to those with tumors that were HALow.

    Methods: This is an ongoing phase II, open-label, randomized study of PEGPH20 +Nab-Paclitaxel （Nab） + Gem （PAG） vs. Nab + Gem （AG） in previously untreated pts with Stage IV PDA. Pts receive 3 ?g/kg twice weekly （Cycle 1） and then weekly （Cycle 2+） PEGPH20 in combination with standard dosing of AG. HA status was tested retrospectively. Primary endpoint is PFS, secondary endpoints include: ORR, OS and Safety. Due to a temporary clinical hold, ORR is from data through April 2014; and PFS is data through December 2014.

    Results: 146 pts were enrolled and 135 pts received at least one dose of study drug. The mean age was 65.1 yrs. （Range 29-83 yrs）， 93% had a KPS of ≥ 80. The most common AEs related to study drugs （PAG vs. AG） were: fatigue （68% vs. 69%）， nausea （55% vs. 44%）， anemia （42% vs. 53%） pe**heral edema （58% vs. 31%） and muscle spasms （55% vs. 2%）。 There was an imbalance of thromboembolic （TE） events with 42% vs. 25% of subjects having at least one TE event. Overall RR and PFS are shown in the table below.
 

    Conclusions: PEGPH20 + Nab/Gem is generally well tolerated in advanced PDA. Patients with HAhigh tumors receiving PAG had greater ORR and longer PFS than HAhigh patients receiving AG. Overall survival will be presented at the time of the meeting. ClinicalTrials.gov Identifier NCT01839487. Clinical trial ***rmation: NCT01839487