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Palbociclib-II期临床试验
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版权所有 不得转载輝瑞正式向美國FDA提交乳腺癌新藥Palbociclib新藥申請
　　大智慧阿思達克通訊社8月19日訊，美國輝瑞於周一宣布，公司已經向美國食品藥品監督管理局（FDA）正式提交Palbociclib的新藥申請（NDA），新藥申請審核為60天。
　　此次輝瑞提交的是Palbociclib聯合來曲唑(Letrozole)用藥，其適應症為雌激素受體陽性、HER2陰性的晚期乳腺癌。申請提交是基於公司臨床II期研究。
　　Palbociclib是一種新型口服CDKs-4和CDKs-6抑制劑，通過重新獲得細胞周期把控，起到阻止癌細胞擴散的作用。該藥物於2013年4月被美國FDA授予「突破性療法」認證。該藥物已經進入2項臨床III期試驗。
　　發稿：張鈞煒/何巨驫 審校：陸晉源/沈瑋
　　*本文信息僅供參考，投資者據此操作風險自擔。
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作者：tomato
来源：生物谷
关键词：辉瑞,palbociclib,CDK46抑制剂,乳腺癌
日讯 /BIOON/ --（Pfizer）4月6日公布了实验性抗癌药palbociclib一项II期研究（PD-0332991）的数据。该项研究在绝经后女性雌激素受体阳性（ER+）、人表皮生长因子受体2阴性（HER2-）局部晚期或转移性患者中开展，研究数据表明，与标准治疗药物曲唑（letrozole）治疗组相比，palbociclib+letrozole联合用药组疾病无进展生存期（PFS）取得了统计学意义的显著延长（20.2个月vs 10.2个月，p=0.0004），达到了研究的主要终点。最终PFS分析时的总生存期（OS）初步数据表明，联合用药组平均总生存期为37.5个月，letrozole治疗组为33.3个月，无统计学显著差异。后续将开展完整的OS分析。研究中，联合用药组耐受性和安全性良好。相关数据已提交至癌症研究协会2014年年会（AACR-2014）。
palbociclib是一种实验性、口服、靶向性制剂，能够选择性抑制细胞周期蛋白依赖性激酶4和6（CDK4/6），恢复细胞周期控制，阻断肿瘤细胞增殖。此前，于2013年4月授予palbociclib治疗晚期或转移性ER+/HER2-乳腺癌的突破性疗法认定。
竞争对手（Novartis）已于去年11月将其CDK4/6抑制剂LEE011推进至III期研究，（Eli Lilly）的药物LY2835219的推进则相对缓慢，研究进程落后于辉瑞和。（生物谷）
英文原文：Pfizer’s Novel CDK 4/6 Inhibitor Palbociclib plus Letrozole Significantly Prolonged Progression-Free Survival in Patients with Advanced Breast Cancer
Final Phase 2 PALOMA-1 Data to Be Presented Today for Potential First-in-Class Palbociclib
Webcast of Conference Call with Securities Analysts to Review Data Scheduled for Today at 1:30 PDT
NEW YORK, N.Y., April 6 C Pfizer Inc. today announced detailed results from the PALOMA-1 study, a randomized Phase 2 study of palbociclib (PD-0332991) in combination with letrozole. PALOMA-1 achieved its primary endpoint by significantly prolonging progression-free survival (PFS) compared with letrozole alone in post-menopausal women with estrogen receptor positive (ER+), human epidermal growth factor receptor 2 negative (HER2-) locally advanced or metastatic breast cancer. For women treated with the combination of palbociclib plus letrozole, the median PFS was 20.2 months, a statistically significant improvement compared to the 10.2 months of PFS in women who received letrozole alone (HR=0.488 [95% CI: 0.319, 0.748]; p=0.0004). These data will be presented today by Dr. Richard S. Finn, associate professor of medicine at University of California, Los Angeles (UCLA) at the American Association of Cancer Research (AACR) Annual Meeting 2014 in San Diego (Abstract #CT101).
"These data demonstrate the potential of palbociclib to be a major advance in the treatment of women with this type of advanced breast cancer," said Dr. Mace Rothenberg, senior vice president of Clinical Development and Medical Affairs and chief medical officer for Pfizer Oncology. "We are proud to be at the forefront of research and development with respect to this promising new class of investigational anticancer agents and have initiated a broad clinical development program for palbociclib that includes breast and non-breast cancers.”
Final results for the secondary efficacy endpoints of duration of treatment and clinical benefit rate demonstrated superiority in the palbociclib plus letrozole arm compared to the letrozole-only arm. Per the PALOMA-1 trial protocol, an initial assessment of overall survival (OS), a secondary endpoint, was also performed. Based on the events at the time of the assessment, a median OS of 37.5 months was observed in the combination arm versus 33.3 months for those who received letrozole alone, a difference of 4.2 months (HR = 0.813, 95% CI: 0.492, 1.345). This OS observation at the time of final PFS analysis was not statistically significant. A follow-up OS analysis will be conducted following the accrual of additional events.
The combination of palbociclib and letrozole was generally well-tolerated and the safety profile of the combination was consistent with previously reported data. The most common adverse events in the palbociclib plus letrozole arm were neutropenia (a decrease of the neutrophil count), leukopenia (a decrease in the total white blood cell count), fatigue and anemia. The neutropenia observed with the combination in this study was non-cumulative and clinically manageable. No cases of febrile neutropenia were reported in either arm of the study. Neutropenia is an on-target, anti-proliferative side effect of palbociclib and signifies inhibition of CDK4 and its effect on bone marrow.
Palbociclib received Breakthrough Therapy designation from the United States Food and Drug Administration (FDA) in April 2013, for the initial treatment of women with advanced or metastatic ER+, HER2- breast cancer. This designation was based on interim data from the PALOMA-1 trial. Pfizer continues to work with the
and other regulatory authorities to define the appropriate regulatory path forward for palbociclib.
Pfizer invites investors and the general public to view and listen to a webcast of a presentation by Pfizer’s Oncology leadership today at 1:30 p.m. Pacific Daylight Time, in connection with the presentation of the final results of PALOMA-1. To view and listen to the webcast, visit our website at
and click on the “Review of Palbociclib Phase 2 PALOMA-1 Results at AACR Annual Meeting 2014” webcast link in the For Investors section located on the lower right-hand corner of that page.
About PALOMA-1
PALOMA-1 (also known as Study 1003 and TRIO-18) is a Phase 2 trial designed to assess PFS in post-menopausal women with ER+, HER2- advanced breast cancer receiving palbociclib (125 mg once daily for three out of four weeks in repeated cycles) in combination with letrozole versus letrozole alone (2.5 mg once daily on a continuous regimen). This trial consisted of two parts. Part 1 enrolled 66 patients with ER+, HER2- advanced breast cancer. Part 2 enrolled 99 additional patients whose tumors were selected for presence of biomarkers: cyclin D1 amplification and/or p16 loss. Final results from PALOMA-1 showed that statistically significant improvement in PFS was achieved for the study arm (palbociclib + letrozole) in both Parts 1 and 2. PFS is comprised of time from randomization to time of disease progression or death from any cause.
PALOMA-1 is conducted in collaboration with the Jonsson Cancer Center’s Revlon/UCLA Women’s Cancer Research Program, led by Dr. Dennis Slamon. PALOMA-1 is a multi-center trial with 101 global sites participating.
Palbociclib Development Program in ER+, HER2- Breast Cancer
Pfizer has worked closely with investigators and international breast cancer experts to establish a robust development program for palbociclib in ER+, HER2- breast cancer across stages and treatment settings.
Pfizer has initiated two Phase 3 studies of palbociclib in advanced/metastatic breast cancer. PALOMA-2 (also known as Study 1008) is a randomized (2:1), multi-center, double blind Phase 3 study that evaluates palbociclib in combination with letrozole versus letrozole plus placebo as a first-line treatment for post-menopausal patients with ER+, HER2- advanced breast cancer. PALOMA-3 (also known as Study 1023) is a randomized (2:1), multi-center, double blind Phase 3 study that evaluates palbociclib in combination with fulvestrant versus fulvestrant plus placebo in women with hormone receptor-positive (HR+), HER2- metastatic breast cancer whose disease has progressed after prior endocrine therapy.
Additional, investigator-led studies of palbociclib in advanced/metastatic breast cancer and in early breast cancer are open and enrolling patients, including the PEARL and PENELOPE-B studies. PEARL, sponsored by Grupo Espa&ol de Investigación en Cáncer de Mama (GEICAM, Spanish Breast Cancer Research Group), with participation from the Central European Cooperative Oncology Group (CECOG), is a randomized (1:1), multi-center, open-label Phase 3 study evaluating palbociclib in combination with exemestane versus capecitabine in post-menopausal women with ER+, HER2- metastatic breast cancer whose disease was refractory to previous non-steroidal aromatase inhibitors (letrozole or anastrozole). PENELOPE-B is a randomized (1:1), double blind, placebo-controlled Phase 3 study comparing palbociclib plus standard endocrine therapy to placebo plus standard endocrine therapy in patients with HR+, HER2-normal (also known as HER2-) early-stage breast cancer with certain features that suggest an increased risk for recurrence after completing pre-operative chemotherapy followed by surgery. This international study is sponsored by the German Breast Group (GBG).
For more information on these and other ongoing clinical trials of palbociclib in breast cancer and other tumor types, please visit .
About Palbociclib
Palbociclib is an investigational oral targeted agent that selectively inhibits cyclin-dependent kinases (CDKs) 4 and 6 to regain cell cycle control and block tumor cell proliferation.
Loss of cell cycle control is a hallmark of cancer and CDK 4/6 are overactivated in numerous cancers, leading to loss of proliferative control. , CDK 4/6 are key regulators of the cell cycle that trigger cellular progression from growth phase (G1) into phases associated with DNA replication (S). , CDK 4/6, whose increased activity is frequent in estrogen receptor-positive (ER+) breast cancer (BC), are key downstream targets [1]&&
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