Pfizer Unveils Positive Results from Asian Subgroup Analysis of ARCHER 1050

辉瑞公布潜力一线肺癌新药数据,ARCHER效果显著

2019-11-25 08:35:00 YAHOO!FINANCE

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Pfizer Inc. (NYSE: PFE) today announced the efficacy and tolerability results from the subgroup analysis of Asian patients enrolled in the ARCHER 1050, a randomized, multicenter, multinational, open-label Phase 3 study evaluating the efficacy of VIZIMPRO® (dacomitinib) - an epidermal growth factor inhibitor (EGFR) tyrosine kinase inhibitor (TKI) - as first-line monotherapy in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with EGFR-activating mutations. The results, which were announced at ESMO Asia Congress 2019, show significant prolongation of progression-free survival (PFS); and an extended follow-up demonstrated significant improvement in overall survival (OS) with first-line dacomitinib versus gefitinib in Asian patients with EGFR-positive advanced NSCLC. The subgroup analysis involved a subset of 346 Asian patients who were enrolled in Mainland China, Hong Kong SAR, Japan and Korea. Data cutoff dates were July 29, 2016 for the PFS analysis and May 13, 2019 for the extended OS analysis. When treated with first-line VIZIMPRO®, the subgroup of Asian patients achieved significant prolongation of PFS (as determined by blinded Independent Radiologic Central (IRC) review) compared with gefitinib (HR = 0.509 [95% CI: 0.391, 0.662], 2-sided p<0.0001). Patients who were randomized to receive once-daily VIZIMPRO® achieved a median PFS of 16.5 months (95% CI: 12.9, 18.4) compared with 9.3 months (95% CI: 9.2, 11.0) in the gefitinib arm.[1] In 2017, the analysis of the intent-to-treat population of ARCHER 1050 reported that the median PFS was 14.7 months in the VIZIMPRO® group (95% CI: 11.1, 16.6) versus 9.2 months (95% CI: 9.1, 11.0) in the gefitinib group.[2] The Asian subgroup analysis presented today demonstrates that treatment with first-line dacomitinib results in significant prolongation of PFS compared with gefitinib in Asian patients. "The results from the current subgroup analysis provide us with a more robust confirmation of the efficacy of dacomitinib as a first-line treatment option for Asian patients with EGFR-positive advanced NSCLC," said Professor Tony Shu Kam Mok, Chairman of the Department of Clinical Oncology, and Li Shu Fan, Medical Foundation Professor of Clinical Oncology of the Faculty of Medicine at The Chinese University of Hong Kong, who presented the results. An extended follow-up of the Asian subgroup (median of 47.9 months for both treatment arms) demonstrated that dacomitinib resulted in significant improvements in the secondary efficacy endpoints of OS and duration of response (DoR) versus gefitinib. Median OS was 37.7 months (95% CI: 30.2, 44.7) for dacomitinib patients versus 29.1 months for gefitinib (95% CI: 25.6, 36.0) (HR for OS = 0.759 [95% CI: 0.578, 0.996] favoring VIZIMPRO®). Median DoR in the VIZIMPRO® group was double that of the gefitinib group (16.6 months [95% CI: 13.8, 30.4] versus 8.3 months [95% CI: 8.1, 10.2], respectively). Significantly, this OS benefit was maintained in patients who had a dose reduction. "We reported, in both the intent-to-treat population as well as the Asian subgroup, that OS benefit was maintained in patients who had a dose modification with dacomitinib at 30mg or 15mg QD. This is important as dose modification is the most effective way to manage toxicity, thereby enabling therapy to be better tolerated without compromising on efficacy of treatment," said Professor Mok. The Asian subgroup analysis also showed that VIZIMPRO® had longer duration of treatment (DoT) compared with gefitinib (77.9 weeks vs. 52.7 weeks). Similar to the as-treated population of ARCHER 1050, the most commonly observed adverse events (AEs) in VIZIMPRO®-treated patients of this Asian subgroup were diarrhea (90.6%), paronychia (64.7%) and dermatitis acneiform (56.5%). No clinically relevant differences in overall frequency of all-cause AEs were observed between the Asian subgroup and the as-treated patient population. Overall, the rates of dose reductions or dosing interruptions were similar in both the Asian subgroup and the as-treated population. About VIZIMPRO® (dacomitinib), 45 mg, 30 mg and 15 mg tablets VIZIMPRO is an oral, once-daily, irreversible pan-human epidermal growth factor receptor kinase inhibitor. VIZIMPRO is approved in Canada, Mainland China, European Union (EU), Hong Kong SAR, Japan, Switzerland and the United States (US) for the first-line treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR)-activating mutations (exon 19 deletion or exon 21 L858R substitution mutations as detected by an FDA-approved test). The applications in the Mainland China, Japan, and the US were reviewed under the Priority Review program. VIZIMPRO is approved in the US for the first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 19 deletion or exon 21 L858R substitution mutations as detected by an FDA-approved test.  In 2012, Pfizer and SFJ Pharmaceuticals entered into a collaborative development agreement to conduct ARCHER 1050 across multiple sites. SFJ is a global drug development company, which provides a unique and highly customized co-development partnering model for the world's top pharmaceutical and biotechnology companies. Under the terms of this agreement, SFJ Pharmaceuticals provided the funding and conducted the trial to generate the clinical data used to support this application. Pfizer retains all rights to commercialize VIZIMPRO globally. About ARCHER 1050 The efficacy of VIZIMPRO was demonstrated in ARCHER 1050, a global Phase 3 head-to-head trial conducted in patients with unresectable, metastatic or recurrent non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) exon 19 deletion or exon 21 L858R substitution mutations, with no prior therapy for metastatic disease or recurrent disease with a minimum of 12 months disease-free after completion of systemic therapy. A total of 452 patients were randomized 1:1 to VIZIMPRO 45 mg (n=227) or gefitinib 250 mg (n=225). Randomization was stratified by region and EGFR mutation status. The primary endpoint of the study was progression-free survival (PFS) as determined by blinded Independent Radiology Central (IRC) review. Key secondary endpoints included PFS assessed by the investigator, objective response rate (ORR), duration of response (DoR), duration of treatment (DoT), overall survival (OS), and patient-reported outcomes (PROs). VIZIMPRO® (dacomitinib) IMPORTANT SAFETY INFORMATION FROM THE U.S. PRESCRIBING INFORMATION There are no contraindications for VIZIMPRO. Interstitial Lung Disease (ILD): Severe and fatal ILD/pneumonitis occurred in patients treated with VIZIMPRO and occurred in 0.5% of the 394 VIZIMPRO-treated patients; 0.3% of cases were fatal. Monitor patients for pulmonary symptoms indicative of ILD/pneumonitis. Withhold VIZIMPRO and promptly investigate for ILD in patients who present with worsening of respiratory symptoms which may be indicative of ILD (e.g., dyspnea, cough, and fever). Permanently discontinue VIZIMPRO if ILD is confirmed. Diarrhea: Severe and fatal diarrhea occurred in patients treated with VIZIMPRO. Diarrhea occurred in 86% of the 394 VIZIMPRO-treated patients. Grade 3 or 4 diarrhea was reported in 11% of patients and 0.3% of cases were fatal. Withhold VIZIMPRO for Grade 2 or greater diarrhea until recovery to less than or equal to Grade 1 severity, then resume VIZIMPRO at the same or a reduced dose depending on the severity of diarrhea. Promptly initiate anti-diarrheal treatment (loperamide or diphenoxylate hydrochloride with atropine sulfate) for diarrhea. Dermatologic Adverse Reactions: Rash and exfoliative skin reactions occurred in patients treated with VIZIMPRO. Rash occurred in 78% of the 394 VIZIMPRO-treated patients. Grade 3 or 4 rash was reported in 21% of patients. Exfoliative skin reactions of any severity were reported in 7% of patients. Grade 3 or 4 exfoliative skin reactions were reported in 1.8% of patients. Withhold VIZIMPRO for persistent Grade 2 or any Grade 3 or 4 dermatologic adverse reaction until recovery to less than or equal to Grade 1 severity, then resume VIZIMPRO at the same or a reduced dose depending on the severity of the dermatologic adverse reaction. The incidence and severity of rash and exfoliative skin reactions may increase with sun exposure. At the time of initiation of VIZIMPRO, initiate use of moisturizers and appropriate measures to limit sun exposure. Upon development of Grade 1 rash, initiate treatment with topical antibiotics and topical steroids. Initiate oral antibiotics for Grade 2 or more severe dermatologic adverse reactions. Embryo-Fetal Toxicity: VIZIMPRO can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to the fetus. Advise females of reproductive potential to use effective contraception during treatment with VIZIMPRO and for at least 17 days after the final dose. Adverse Reactions: The most common (>20%) adverse reactions were diarrhea (87%), rash (69%), paronychia (64%), stomatitis (45%), decreased appetite (31%), dry skin (30%), decreased weight (26%), alopecia (23%), cough (21%), and pruritus (21%). The most common (more than or equal to 1%) serious adverse reactions were diarrhea (2.2%) and interstitial lung disease (1.3%). Drug Interactions: Concomitant use with a proton pump inhibitor (PPI) decreases dacomitinib concentrations, which may reduce VIZIMPRO efficacy. Avoid the concomitant use of PPIs with VIZIMPRO. As an alternative to PPIs, use locally-acting antacids or an H2-receptor antagonist. Administer VIZIMPRO at least 6 hours before or 10 hours after taking an H2-receptor antagonist. Concomitant use of VIZIMPRO increases the concentration of drugs that are CYP2D6 substrates which may increase the risk of toxicities of these drugs. Avoid concomitant use of VIZIMPRO with CYP2D6 substrates where minimal increases in concentration of the CYP2D6 substrate may lead to serious or life-threatening toxicities. Lactation: Because of the potential for serious adverse reactions in breastfed infants from VIZIMPRO, advise women not to breastfeed during treatment with VIZIMPRO and for at least 17 days after the last dose. Hepatic Impairment: No dose adjustment is recommended in patients with mild or moderate hepatic impairment. The recommended dose of VIZIMPRO has not been established for patients with severe hepatic impairment. Renal Impairment: No dose adjustment is recommended for patients with mild or moderate renal impairment. The recommended dose of VIZIMPRO has not been established for patients with severe renal impairment. Please see full prescribing information at Pfizer.com [1] Pfizer. Data on file. [2] Wu YL, Cheng Y, Zhou X, et al. Dacomitinib versus gefitinib as first-line treatment for patients with EGFR-mutation-positive non-small-cell lung cancer (ARCHER 1050): a randomised, open-label, phase 3 trial. Lancet Oncol. 2017;18(11):1454-1466. About Non-Small Cell Lung Cancer Lung cancer is the most common cancer worldwide, with more than two million new cases diagnosed globally in 2018.1 About 85 percent of all lung cancers are identified as non-small cell, and approximately 75 percent of these are metastatic, or advanced, at diagnosis. EGFR is a protein that helps cells grow and divide. When the EGFR gene is mutated it can cause the protein to be overactive resulting in cancer cells to form. EGFR mutations may occur in 10 to 35 percent of NSCLC tumors globally, and the most common activating mutations are deletions in exon 19 and exon 21 L858R substitution, which together account for more than 80 percent of known activating EGFR mutations. The disease is associated with low survival rates and disease progression remains a challenge. About Pfizer in Lung Cancer Pfizer Oncology is committed to addressing the unmet needs of patients with lung cancer, the leading cause of cancer-related deaths worldwide and a particularly difficult-to-treat disease. Pfizer strives to address the diverse and evolving needs of patients with non-small cell lung cancer (NSCLC) by developing efficacious and tolerable therapies, including biomarker-driven therapies. By combining leading scientific insights with a patient-centric approach, Pfizer is continually advancing its work to match the right patient with the right medicine at the right time. Through our research and collaboration efforts, we are committed to delivering renewed hope to patients living with NSCLC. About Pfizer Oncology At Pfizer Oncology, we are committed to advancing medicines wherever we believe we can make a meaningful difference on the lives of patients. Today, Pfizer Oncology has an industry-leading portfolio of 22 approved innovative cancer medicines and biosimilars across more than 30 indications, including breast, prostate, kidney and lung cancers, as well as leukemia and melanoma. SOURCE Pfizer
辉瑞(Pfizer)公司(纽约证券交易所: PFE )今天公布了 ARCHER 1050亚洲患者分组分析的疗效和耐受性结果, ARCHER 1050是一个随机、多中心、多国开放标签第3期研究评估了 VIZMPRO ®( dacitinib )——表皮生长因子抑制剂( EGFR )酪氨酸激酶抑制剂( TKI )——作为一线单药治疗局部晚期或转移性非小细胞肺癌( NSCLC )与 EGFR 激活突变的疗效。这一结果在2019年 ESMO 亚洲大会上公布,显示无进展生存期( PFS )显著延长;扩展随访显示,在 EGFR 阳性的晚期非小细胞非小细胞肺癌(NSCLC)患者中,一线达布替尼与吉非替尼的整体生存期( OS )显著改善。 该亚组分析涉及346名亚洲患者的一个子集,他们分别在中国大陆、香港特别行政区、日本和韩国注册。数据截止日期为2016年7月29日,用于 PFS 分析,2019年5月13日用于扩展 OS 分析。 在一线 VIZMPRO ®治疗时,亚洲患者的亚组与吉非替尼( HR =0.509[95% CI :0.391,0.662],2侧 p <0.0001)相比, PFS 明显延长(由盲性独立放射学中心( IRC )检查确定)。随机接受每日一次 VIZMPRO ®治疗的患者的 PFS 中值为16.5个月(95% CI :12.9,18.4),而吉非替尼手臂的 PFS 中值为9.3个月(95% CI :9.2,11.0)。[1] 2017年,对 ARCHER 1050有意治疗人群的分析报告显示, VIZMPRO ®组的 PFS 中值为14.7个月(95% CI :11.1,16.6),而吉非替尼组的 PFS 中值为9.2个月(95% CI :9.1,11.0)。[2]今天提出的亚洲亚组分析表明,与 GEfitinib 相比,一线 dacitinib 治疗可显著延长 PFS 。临床肿瘤学系系主任 Tony Shu Kam Mok 教授和 Li Shu Fan 教授说:“目前的亚组分析结果为我们提供了更有力的证据,证明达力替尼作为治疗 EGFR 阳性的晚期非小细胞非小细胞肺癌(NSCLC)的一线治疗方案的疗效。”香港中文大学医学院临床肿瘤学医学基金会教授,他介绍了研究结果。 亚洲亚组(两个治疗臂的中位数为47.9个月)的长期随访表明,达比替尼可显著改善 OS 次要疗效终点和反应持续时间( DoR )对吉非替尼的疗效。中位 OS 为37.7个月(95% CI :30.2,44.7),而吉非替尼为29.1个月(95% CI :25.6,36.0)( HR for OS =0.759[95% CI :0.578,0.996]有利于 VIZMPRO ®)。VIZMPRO ®组中的中间 DoR 是吉非替尼组的两倍(16.6个月[95% CI :13.8,30.4],而8.3个月[95% CI :8.1,10.2])。 值得注意的是,在剂量减少的患者中,这种 OS 益处得到了维持。“我们报告说,不管是有意治疗的人群还是亚洲亚组,服用达布替尼剂量为30mg 或15mg QD 的患者维持 OS 疗效。这一点很重要,因为剂量改变是控制毒性的最有效方法,从而使治疗在不损害治疗效果的情况下更好地耐受。 亚洲亚组分析还显示,相比吉非替尼(77.9周,52.7周), VIZMPRO ®治疗时间( DoT )更长。与接受治疗的 ARCHER 1050人群相似, VIZIMMPRO ®治疗的亚洲亚组患者中最常见的不良事件( AEs )为腹泻(90.6%)、腮腺炎(64.7%)和皮炎痤疮(56.5%)。亚洲亚组与接受治疗的患者总体 AE 频率无临床相关差异。总体而言,亚洲亚组和接受治疗的人群的剂量减少或剂量中断的发生率相似。 约 VIZIMMPRO ®( dacitinib ),45毫克,30毫克和15毫克片剂 VIZMPRO 是一种口服的,每日一次的,不可逆转的全人表皮生长因子受体激酶抑制剂。VIZINMPRO 在加拿大、中国大陆、欧盟、香港特别行政区、日本瑞士和美国(美国)用于一线治疗成人晚期或转移性非小细胞肺癌( NSCLC )患者的表皮生长因子受体( EGFR )激活突变(外显子19缺失或外显子21L858R 替代突变,由 FDA 批准的检测)。中国大陆、日本和美国的申请根据优先审查计划进行了审查。 VIZMPRO 在美国被批准用于一线治疗具有表皮生长因子受体( EGFR )外显子19缺失或外显子21L858R 替代突变的转移性非小细胞肺癌( NSCLC )患者,该突变由 FDA 批准的试验检测。 2012年,辉瑞(Pfizer)与 SFJ 制药达成合作开发协议,在多个地点开展 ARCHER 1050。SFJ 是一家全球性的药物开发公司,为全球顶尖的制药和生物技术公司提供独特的、高度定制化的合作开发模式。根据本协议条款, SFJ 药业提供资金并进行试验,生成用于支持本申请的临床数据。辉瑞(Pfizer)保留在全球商业化 VIZMPRO 的所有权利。 约1050 VIZMPRO 的疗效在 ARCHER 1050中得到了证实。 ARCHER 1050是一项全球3期的头到头试验,用于携带表皮生长因子受体( EGFR )外显子19缺失或外显子21L858R 替换突变的非小细胞肺癌( NSCLC )患者。在完成系统治疗后,至少12个月无疾病的转移性疾病或复发性疾病的早期治疗。共有452例患者随机分为1:1至 VIZMPRO 45 mg ( n =227)或吉非替尼250 mg ( n =225)。随机分组按区域和 EGFR 突变状态进行分层。这项研究的主要终点是无进展生存( PFS ),由盲性独立放射学中心( IRC )审查确定。主要的次要终点包括研究者评估的 PFS 、客观反应率( ORR )、反应持续时间( DoR )、治疗持续时间( DoT )、总体生存( OS )和患者报告的结果( PRO )。 VIZINMPRO ®( dacitinib )来自美国预存信息的重要安全信息 VIZMPRO 没有禁忌症。 间肺疾病( ILD ):重症和致命性 ILD /肺炎发生在接受 VIZINMPRO 治疗的患者中,394名 VIZINMPRO 治疗的患者中有0.5%发生;0.3%的患者死亡。监测显示 ILD /肺炎的肺部症状。停用 VIZINMPRO ,并迅速对可能提示 ILD 的呼吸症状恶化(如呼吸困难、咳嗽和发烧)的患者进行 ILD 调查。如果 ILD 被确认,则永久停止 VIZINMPRO 。 腹泻:使用 VIZMPRO 治疗的患者出现严重和致命的腹泻.394名接受 VIZMPRO 治疗的患者中有86%发生腹泻。11%的患者出现3~4级腹泻,0.3%的患者死亡.停用 VIZMPRO 治疗2级或更大的腹泻直至恢复到小于或等于1级严重程度,然后根据腹泻的严重程度恢复相同或减少剂量的 VIZMPRO 。及时启动抗腹泻治疗(阿托品硫酸吡咯胺或二苯氧酸盐)腹泻。 皮肤不良反应:在接受 VIZMPRO 治疗的患者中发生 Rash 和剥落皮肤反应。在394名接受 VIZMPRO 治疗的患者中,有78%发生 Rash 。21%的患者出现3级或4级皮疹。7%的患者出现任何严重程度的脱皮反应。3级或4级剥落皮肤反应的报告在1.8%的患者。在恢复到低于或等于1级严重程度之前,暂停2级或3级或4级皮肤不良反应的 VIZMPRO ,然后根据皮肤不良反应的严重程度恢复相同剂量或减少剂量的 VIZMPRO 。皮疹和剥落皮肤反应的发生率和严重程度可能随着阳光照射而增加。在启动 VIZINMPRO 的时候,开始使用保湿剂和适当的措施来限制阳光的暴露。一旦出现1级皮疹,开始使用外用抗生素和外用类固醇治疗。引发2级以上严重皮肤病不良反应的口服抗生素. 胚胎-胎儿毒性: VIZINMPRO 在给孕妇服用时会造成胎儿伤害。建议孕妇注意胎儿的潜在危险。建议有生育潜力的女性在接受 VIZMPRO 治疗期间使用有效的避孕方法,并在最后一次注射后至少17天内使用有效的避孕方法。 不良反应:最常见的不良反应为腹泻(87%)、皮疹(69%)、腮腺炎(64%)、口腔炎(45%)、食欲减退(31%)、皮肤干燥(30%)、体重减轻(26%)、脱发(23%)、咳嗽(21%)和瘙痒(21%)。最常见(超过或等于1%)严重不良反应为腹泻(2.2%)和间质性肺疾病(1.3%)。 药物相互作用:与质子泵抑制剂( PPI )同时使用可以减少 dacitinib 浓度,从而降低 VIZMPRO 的疗效。避免与 VIZMPRO 同时使用 PPI 。作为 PPI 的替代品,使用局部作用的抗酸剂或 H2受体拮抗剂。至少在服用 H2受体拮抗剂前6小时或10小时后服用 VIZMPRO 。同时使用 VIZMPRO 可以增加 CYP2D6底物的药物浓度,从而增加这些药物的毒性风险。避免同时使用 VIZMPRO 和 CYP2D6底物,其中 CYP2D6底物浓度的最小增加可能导致严重或危及生命的毒性。 哺乳:由于可能严重不良反应的母乳喂养婴儿从 VIZMPRO ,建议妇女不要母乳喂养期间与 VIZMPRO 治疗和至少17天后,最后一次剂量。 肝损害:轻、中度肝损害患者不建议进行剂量调整.推荐剂量的 VIZMPRO 还没有确定的严重肝损害患者。 肾脏损害:对于轻度或中度肾损害的患者不建议进行剂量调整.推荐剂量的 VIZMPRO 尚未确定的严重肾损害患者。 请参阅辉瑞(Pfizer)公司的处方信息。com [1]辉瑞(Pfizer)公司。文件上的数据。 [2]吴仪、郑Y 、周X 等。达莫西替尼与吉非替尼作为 EGFR 突变阳性非小细胞肺癌( ARCHER 1050)的一线治疗方案:随机、开放标签、3期试验。Lancet Oncol 。2017年;18(11):1454-1466。 非小细胞肺癌的研究 肺癌是全球最常见的癌症,2018年全球新诊断病例达200多万。1约85%的肺癌被确认为非小细胞,其中约75%是转移性或晚期肺癌。 EGFR 是一种帮助细胞生长和分裂的蛋白质。当 EGFR 基因发生突变时,它会导致蛋白质过度激活,导致癌细胞形成。EGFR 突变可能发生在全球10%至35%的非小细胞非小细胞肺癌(NSCLC)中,最常见的激活突变是外显子19和外显子21L858R 的缺失,这两种突变加起来占已知活化 EGFR 突变的80%以上。该疾病与低存活率和疾病进展仍然是一个挑战。 关于肺癌的辉瑞(Pfizer)公司 辉瑞(Pfizer)肿瘤公司致力于解决肺癌患者未得到满足的需求,肺癌是全球癌症相关死亡的主要原因,也是一种特别难以治疗的疾病。辉瑞(Pfizer)致力于通过开发有效且可耐受的治疗方法,包括生物标志物驱动的治疗方法,满足非小细胞肺癌( NSCLC )患者的多样化和不断发展的需求。通过将领先的科学见解与以病人为中心的方法相结合,辉瑞(Pfizer)不断推进其工作,以便在合适的时间将合适的病人与合适的药物相匹配。通过我们的研究和合作,我们致力于为非小细胞非小细胞肺癌(NSCLC)患者提供新的希望。 关于辉瑞(Pfizer)肿瘤学 在辉瑞(Pfizer)肿瘤学公司,我们致力于在我们认为能够对患者生活产生重大影响的任何地方推广药物。今天,辉瑞(Pfizer)肿瘤学拥有行业领先的22种已批准的创新癌症药物和生物仿制药类似物,涉及30多个适应症,包括乳腺癌、前列腺癌、肾癌和肺癌,以及白血病和黑色素瘤。 辉瑞(Pfizer)制药公司

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