——欧盟批准罗氏单抗Perjeta用于HER2阳性乳腺癌新辅助治疗
2015年7月31日，欧盟委员会（EC）批准抗癌药Perjeta（pertuzumab）联合赫赛汀（Herceptin）及化疗，用于局部晚期、炎症性或伴有复发高风险的HER2阳性早期乳腺癌（eBC）成人患者的新辅助治疗（术前治疗）。此次批准，使Perjeta方案成为欧盟基于病理完全缓解（pCR）数据批准的首个乳腺癌新辅助治疗方案。之前，Perjeta已获美国及其他21个国家批准，用于HER2阳性早期乳腺癌（eBC）的新辅助治疗。
据估计，在欧盟每年确诊HER2阳性乳腺癌的病例高达10万例，这是一种比HER2阴性乳腺癌更具侵略性的乳腺癌类型。在肿瘤扩散前对早期乳腺癌患者进行治疗，可以提高预防疾病复发的机会。
一直以来，肿瘤的有效治疗手段都是以手术切除为主，除外科手术之外的治疗均称为辅助治疗。新辅助治疗（neoadjuvant therapy）是指在手术治疗前实施的治疗措施，主要包括化疗和放疗，其目的是减小肿瘤的体积，使其能够更容易手术移除。病理完全缓解（pCR）是指在开展外科手术时受影响的乳房或乳房及局部淋巴结中检测不到肿瘤组织，即无癌状态（cancer-free）。这是评估乳腺癌新辅助治疗效果的一种常规手段，在早期乳腺癌（eBC）临床治疗中相比传统终点评估的更快。
Perjeta的获批，主要基于新辅助治疗（neoadjuvant）II期NeoSphere研究的数据，数据显示，接受Perjeta+赫赛汀+多西紫杉醇化疗方案的患者组，有近40%的患者实现病理完全缓解（pCR），而赫赛汀+多西紫杉醇化疗组实现pCR的比例为21.5%。同时，该批准也得到II期TRYPHAENA研究的支持，数据显示，接受Perjeta新辅助治疗的3个组pCR数据为54.7-63.6%。此外，该批准得到了初治HER2阳性晚期乳腺癌患者中开展的III期CLEOPATRA研究提供的长期安全性数据支持。另外，正在开展的辅助治疗（术后）III期APHINITY研究，将为HER2阳性早期乳腺癌（eBC）群体中Perjeta更广阔的应用提供额外的见解。
NeoSphere研究的随访数据也已于今年6月在第51届美国临床肿瘤学会（ASCO）年会上公布。数据显示，与术前接受赫赛汀+化疗方案组相比，术前接受Perjeta+赫赛汀+化疗方案组的患者，经历疾病恶化、复发或死亡的风险降低31%（无进展生存期PFS HR=0.69; 95% CI, 0.34-1.40），经历复发或死亡的风险降低40%（无病生存期DFS HR=0.60; 95% CI, 0.28-1.27）。这些新数据表明，Perjeta新辅助方案的pCR疗效有望转化为对患者预后的长期改善。
New Drugs Online Report for pertuzumab
Information
Generic Name: pertuzumab  
Trade Name: Perjeta 
Synonym: RG1273, Omnitarg 
Entry Type: New molecular entity  
Development and Regulatory status
UK: Launched 
EU: Launched 
US: Launched 
UK launch Plans: Available only to registered users
Actual UK launch date: March 2013 
Comments
Sep 14: Roche will ask regulators around the world to add the CLEOPATRA data to Perjeta´s licence [23].
30/09/2014 11:51:31 
Mar 13: Launched in the UK. Price of one 14 ml vial (420 mg at a concentration of 30 mg/ml) excl VAT is £2395 [18].
15/03/2013 10:27:51 
Mar 13: Approved in the EU [17].
05/03/2013 19:49:00 
Dec 12: CHMP adopted a positive opinion, recommending approval for use in combination with trastuzumab and docetaxel in adult patients with HER2-positive metastatic or locally recurrent unresectable breast cancer, who have not received previous anti-HER2 therapy or chemotherapy for their metastatic disease [16].
15/12/2012 18:11:45 
Jun 12: Launched in the US [14].
06/12/2012 15:20:34 
Jun 12: Perjeta is approved in the US in combination with trastuzumab and docetaxel chemotherapy for the treatment of people with HER2-positive metastatic breast cancer who have not received prior anti-HER2 therapy or chemotherapy for metastatic disease [11}.
11/06/2012 10:48:51 
May 12: US approval decision expected by 8 Jun [10]
16/05/2012 17:39:35 
Feb 12: Filed in EU Dec 11 [8].
18/02/2012 18:44:22 
Feb 12: US FDA granted pertuzumab a Priority Review [7]
09/02/2012 08:20:33 
Dec 10: Data from the PIII study in 1st line HER2-positive metastatic breast cancer, CLEOPATRA, are expected for 2011 [4].
10/12/2010 08:28:31 
Filings planned 2011 [3].
07/09/2010 11:15:33 
PIII study started Jan 08 [1].
22/11/2009 18:43:18 
Trial or other data
Sep 14: Genentech announces final survival results from the PIII CLEOPATRA study, which showed that adding pertuzumab to trastuzumab and docetaxel chemotherapy extended overall survival by 15.7 months vs. trastuzumab and chemotherapy (median OS: 56.5 vs. 40.8 months) [23].
30/09/2014 11:50:13
Dec 13: NCT02019277 is an open-label PIII study of IV pertuzumab, sc trastuzumab, and taxane chemotherapy (docetaxel, paclitaxel or nab-paclitaxel) as first-line therapy in 50 patients with HER2-positive metastatic breast cancer. The study starts Nov 13 and is due to complete May 17 [22]
30/12/2013 10:09:54
Aug 13: NICE draft recommendations advise against routine use of pertuzumab as it us uncertain how long the drug might extend people´s lives yet it costs much more than current NHS treatments [21]. 
07/08/2013 10:47:43
May 13: Listed on the National Cancer Drugs Fund List for treatment of BC [20].
13/05/2013 10:29:41
Apr 13: Updated survival results published in the Lancet. In the ITT, 267 patients died by data cutoff (May 14, 2012), 154 (38%) of 406 in the placebo group and 113 (28%) of 402 in the pertuzumab group. Median OS was 37·6 months (95% CI 34·3—NE [not estimable]) in the placebo group but had not been reached (42·4—NE) in the pertuzumab group (hazard ratio 0·66 [0·52—0·84]; p=0·0008). Investigator-assessed median PFS was 12·4 months (10·4—13·5) in the placebo group and 18·7 months (16·6—21·6) in the pertuzumab group (hazard ratio 0·69; [0·58—0·81]). Serious adverse events were reported in 115 (29%) of 396 patients who received placebo, trastuzumab, and docetaxel and 148 (36%) of 408 who received pertuzumab, trastuzumab, and docetaxel, and included febrile neutropenia, neutropenia, diarrhoea, pneumonia, and cellulitis. Overall, adverse events were similar to those reported at the primary analysis with respect to frequency, severity, and specificity [19].
19/04/2013 10:41:15
Dec 12: Updated survival results reported from the PIII CLEOPATRA study. The combination of pertuzumab, trastuzumab and docetaxel significantly extended overall survival in people with previously untreated HER2-positive mBC vs trastuzumab, chemotherapy and placebo; the risk of death was reduced by 34% (HR=0.66; p=0.0008). At the time of the analysis, median overall survival had not yet been reached in the pertuzumab combination group and was 37.6 months in the control group. Based on these data, the control group has been offered the option to receive pertuzumab. No new safety signals were observed in the study [15].
10/12/2012 09:48:12
Jun 12: Overall survival in the CLEOPATRA study is reported to have crossed the pre-specified boundary showing that the combination of Perjeta, Herceptin and docetaxel chemotherapy significantly improved overall survival in people with HER2-positive mBC, vs Herceptin and chemotherapy. Overall survival is a secondary endpoint of the CLEOPATRA study [13].
23/06/2012 22:28:00
Jun 12: Pertuzumab will be sold as Perjeta in the US at a cost of $5,900 a month, or about $71,000 a year [12].
11/06/2012 21:44:07
Apr 12: NCT01572038 (PERUSE): A PIII multicentre, open-label, single-arm study of pertuzumab + trastuzumab and a taxane in first-line treatment in 1500 patients with metastatic or locally recurrent HER2-positive breast cancer. Patients will receive pertuzumab 840mg iv and trastuzumab 8mg/kg iv + a taxane on Day 1 of Cycle 1, followed by pertuzumab 420mg iv and trastuzumab 6mg/kg iv plus a taxane on Day 1 of each subsequent 3-week cycle. Anticipated time on study treatment is until disease progression or unacceptable toxicity occurs. The primary outcome is the incidence of adverse events. The study started Apr 12 and is due to complete Apr 16 [9].
14/04/2012 23:00:12
Dec 11: CLEOPATRA published online in NEJM 7 Dec. Median PFS was 12.4 mths in the control group vs. 18.5 mths in the pertuzumab gp (hazard ratio for progression or death 0.62 [95% CI 0.51 to 0.75]; p<0.001). The interim analysis could not confirm an overall survival advantage but there was a trend in favour of pertuzumab plus trastuzumab plus docetaxel. The safety profile was generally similar in the two gps, with no increase in left ventricular systolic dysfunction; the rates of febrile neutropenia & diarrhoea of grade 3 or above were higher in the pertuzumab gp than in the control gp [6].
09/12/2011 10:26:13
Jul 11: Top line results reported from the PIII RCT CLEOPATRA (CLinical Evaluation Of Pertuzumab And TRAstuzumab) comparing pertuzumab + trastuzumab + docetaxel vs trastuzumab + docetaxel in 808 treatment naive people with HER2-positive mBC. Pertuzumab was given as a 840mg loading dose followed by 420 mg every three weeks. Patients on triple therapy had longer PFS, the primary endpoint of the study. No new safety signals were observed [5]. 
15/07/2011 15:36:43
Feb 10: in an open-label, single-arm, two-stage study, 66 pts with advanced HER2-positive breast cancer in whom disease progression had occurred during prior trastuzumab-based therapy received trastuzumab (4 mg/kg loading dose, then 2 mg/kg every wk or 8 mg/kg loading dose, then 6 mg/kg every 3 wks) & pertuzumab (840 mg loading dose, then 420 mg every 3 wks). The objective response rate was 24.2%, & the clinical benefit rate was 50%. Five pts (7.6%) experienced a complete response, 11 pts (16.7%) experienced a partial response, and 17 pts (25.8%) experienced stable disease of 6 mths. Median progression-free survival was 5.5 mths. Four pts experienced grade 3 treatment-related AEs; two reports of diarrhoea, one central line infection, & one report of pruritic rash. Cardiac dysfunction was minimal, and no pts withdrew as a result of cardiac-related AEs [2].
03/02/2010 17:10:25
A PIII study evaluating combined Herceptin and pertuzumab plus chemotherapy in first-line metastatic breast cancer began recruiting patients in January 2008 [1].
22/11/2009 18:44:46
Final results from a PII trial in women with pretreated HER2-positive metastatic breast cancer were presented at ASCO 2008. The data showed high response and very good clinical benefit rates for patients who received pertuzumab plus Herceptin [1].
22/11/2009 18:43:43
Evidence Based Evaluations
SMC  NICE scope 
SMC  LNDG 
Available only to registered users