文章來源：
在芝(zhi)加(jia)哥當地(di)時間6月(yue)1日上(shang)午(wu)的(de)(de)(de)ASCO乳腺癌(ai)專場(chang)上(shang)，來自(zi)倫敦癌(ai)癥(zheng)研究(jiu)所的(de)(de)(de)Nicholas C.Turner口頭報告了(le)III期(qi)研究(jiu)PALOMA-3的(de)(de)(de)最新(xin)結果。該(gai)研究(jiu)表明，對(dui)于經治的(de)(de)(de)激素(su)受體(ti)陽性、人(ren)類表皮生長(chang)因子受體(ti)2陰性（HR+/HER2-）的(de)(de)(de)晚(wan)期(qi)乳腺癌(ai)患者，在標準(zhun)的(de)(de)(de)激素(su)治療方案（氟(fu)維司群）中加(jia)入(ru)靶向藥物palbociclib，可以使疾病控(kong)制的(de)(de)(de)時間延長(chang)一(yi)倍以上(shang)，并延遲大約五個月(yue)的(de)(de)(de)疾病進展(zhan)時間（摘要(yao)號，LBA502）。醫脈(mo)通對(dui)此進行了(le)報道。
根據中(zhong)期分析的(de)(de)結果(guo)，這項(xiang)試驗提早終止(zhi)。全部(bu)乳(ru)腺癌(ai)患者中(zhong)大約有75%的(de)(de)患者是激(ji)素受體陽性(xing)（HR+），HER2陰(yin)性(xing)的(de)(de)（HER2-）。對于HR+和HER2-的(de)(de)晚期乳(ru)腺癌(ai)的(de)(de)患者，初(chu)始(shi)雌激(ji)素治(zhi)療(liao)后(hou)，結合(he)了palbociclib的(de)(de)激(ji)素治(zhi)療(liao)方案有可能成為一種非常(chang)有效的(de)(de)治(zhi)療(liao)選擇。
該研(yan)究的主要(yao)作者、皇家馬斯登(deng)醫學腫(zhong)瘤顧問及(ji)倫(lun)敦癌(ai)癥研(yan)究所組長Nicholas C.Turner表示(shi)，“當初始(shi)雌激素治療對轉移性乳腺癌(ai)不起(qi)作用后(hou)，下一(yi)步是典型(xing)的化(hua)療，這通常是有效的，但(dan)是對于女性來說，副作用是難(nan)以承(cheng)受(shou)的”。他說道，“這種相對比較容易接受(shou)的新藥(yao)可以大(da)大(da)延(yan)遲患者需要(yao)開始(shi)化(hua)療的時間(jian)，這是一(yi)個令人(ren)激動的新療法”。
Palbociclib是(shi)一(yi)種新型，阻斷(duan)周期素(su)依賴性(xing)蛋(dan)白激(ji)酶(mei)（CDKs）4和(he)6的(de)口服藥(yao)物。之前的(de)研究表明，CDK4和(he)CDK6是(shi)刺激(ji)激(ji)素(su)受體陽性(xing)乳腺腫瘤生長的(de)關鍵(jian)性(xing)蛋(dan)白。強(qiang)有力(li)的(de)臨床前證(zheng)據支持將CDK4和(he)CDK6抑制劑與激(ji)素(su)治療聯合(he)的(de)方案。對于(yu)HR+和(he)HER2-的(de)晚期乳腺癌(ai)患者來(lai)說，氟維司(si)群是(shi)最有效的(de)激(ji)素(su)治療方案之一(yi)。
HR+和HER2-的女性乳(ru)腺癌患(huan)者(zhe)(zhe)(zhe)被(bei)隨機分配接受palbociclib聯合氟維(wei)(wei)司群治(zhi)療，或安慰劑(ji)聯合氟維(wei)(wei)司群治(zhi)療。所有患(huan)者(zhe)(zhe)(zhe)都(dou)是經(jing)過初(chu)始激(ji)素治(zhi)療后發生疾病惡化(hua)或者(zhe)(zhe)(zhe)復發的轉移性乳(ru)腺癌患(huan)者(zhe)(zhe)(zhe)，并且21%的患(huan)者(zhe)(zhe)(zhe)都(dou)處(chu)在(zai)絕(jue)經(jing)前。根據(ju)研究(jiu)者(zhe)(zhe)(zhe)的報道，PALOMA-3是在(zai)包括絕(jue)經(jing)前年輕女性在(zai)內的晚期乳(ru)腺癌患(huan)者(zhe)(zhe)(zhe)中進(jin)行(xing)，首(shou)個使用靶向治(zhi)療聯合激(ji)素治(zhi)療的注(zhu)冊研究(jiu)。
中期分析顯示，palbociclib組的(de)疾病進展平均時(shi)間為9.2個(ge)(ge)月(yue)，而安慰劑組為3.8個(ge)(ge)月(yue)。類(lei)似(si)的(de)結果也出現在絕經(jing)前(qian)和絕經(jing)后的(de)女(nv)性(xing)。
需要更長時(shi)間(jian)的(de)隨(sui)訪來確(que)定(ding)palbociclib對總生(sheng)存的(de)影響，生(sheng)活質(zhi)量數據的(de)搜集和(he)報道將在之后進行。
Palbociclib聯合治療的(de)耐受性(xing)較好，僅僅只有2.6%的(de)患(huan)者因為副作用而中止治療，最常(chang)見的(de)副作用是血(xue)細胞(bao)計數異(yi)常(chang)。盡(jin)管(guan)頻(pin)繁出現低白(bai)細胞(bao)計數事件，但是發熱性(xing)中性(xing)粒細胞(bao)減(jian)少這種嚴重并發癥發生的(de)比率(lv)非常(chang)低（0.6%）。兩(liang)組(zu)的(de)情況相同。
另一項(xiang)研究PALOMA-2探索了palbociclib用(yong)于未經激素治療的晚期乳腺癌患者的療效。Turner指出，研究人員也在探索運用(yong)這種方式治療早期激素受體(ti)陽性的乳腺癌患者的可能性。
今年早些(xie)時候，FDA加(jia)速批準(zhun)palbociclib聯(lian)合來曲唑(zuo)用于未經激素治療轉(zhuan)移性疾病的(de)(de)ER+和HER2-晚期（轉(zhuan)移性）乳(ru)腺癌(ai)患(huan)者。這項批準(zhun)使基于先(xian)前(qian)的(de)(de)II期試驗PALOMA-1結果。
摘要原文
Background: The growth of hormone receptor (HR) positive breast cancer (BC) is dependent on the cyclin dependent kinases CDK4/6, that promote G1-S phase cell cycle progression. Resistance to endocrine treatment remains a major clinical problem for patients with hormone receptor positive breast cancer. The PALOMA3 study assessed the efficacy of palbociclib and fulvestrant in endocrine-resistant advanced breast cancer.
Methods: In this double-blind phase 3 study women with HR positive/HER2 negative advanced metastatic BC whose cancer had relapsed or progressed on prior endocrine therapy, were randomized 2:1 to palbociclib (Palbo, 125 mg/d orally for 3 wk followed by 1 wk off) and fulvestrant (F, 500 mg per standard of care) or placebo (PLB) and F. Pre- and peri-menopausal women also received goserelin. One previous line of chemotherapy for metastatic disease was permitted. The primary endpoint was investigator assessed progression-free survival (PFS). Secondary endpoints included overall survival (OS), response assessment, patient-reported outcomes, and safety and tolerability. A pre-planned interim analysis was performed after 195 PFS events by an independent data monitoring committee.
Results: 521 pts were randomized, 347 to receive Palbo+F and 174 to PLB+F. Baseline characteristics were well balanced. The median age was 57 and 56 years, 79% were post-menopausal, 60% had visceral disease, and 79% were sensitive to prior endocrine therapy. Prior therapy included chemotherapy for advanced disease in 33% of pts. At the time of the interim analysis the study met the primary endpoint, median PFS was 9.2 months for Palbo+F and 3.8 months for PLB+F (HR 0.422, 95% CI 0.318 to 0.560, P<0.000001). Consistent benefit from Palbo was seen in pre- and post-menopausal women. The most common adverse effects Palbo+F versus PLB+F were neutropenia (78.8% vs. 3.5%), leucopenia (45.5% vs. 4.1%), and fatigue (38.0% vs. 26.7%). Febrile neutropenia was reported in 0.6% pts on Palbo+F and 0.6% pts on PLB+F. The discontinuation rate due to adverse events was 2.0% on Palbo and 1.7% on PLB.
Conclusion: Palbociclib combined with fulvestrant improved progression free survival in hormone receptor positive advanced breast cancer that had progressed on prior endocrine therapy, and can be considered as a treatment option for these patients.