您所在的位置:首頁 > 腫瘤科醫(yī)學進展 > [ASCO2015]LL8:阿法替尼 vs 厄洛替尼用于晚期肺鱗癌的二線治療
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日上午的非小細胞肺癌(NSCLC)口頭報告專場,將公布LUX-Lung8(LL8)研究的總生存期結果,該研究對比了阿法替尼(A)和厄洛替尼(E)用于晚期肺鱗狀細胞癌(SCC)患者二線治療的療效,患者之前接受鉑類為基礎的化療。下面和大家提前分享這項研究的摘要。
背景:晚期肺鱗癌患者在鉑類為基礎的化療之后針對疾病進展的治療方案還比較有限。SCC的病理學發(fā)現(xiàn)EGFR、ErbB受體過表達和下游通路失調參與其中。LL8(肺鱗癌患者二線A vs E;A為不可逆的ErbB家族抑制劑,E為可逆的EGFR酪氨酸激酶抑制劑)的初步分析顯示阿法替尼可帶來更好的無進展生存期(PFS)。本研究報告了OS和更新的PFS數(shù)據(jù)。
方法:IIIB/IV期患者1:1隨機分配接受阿法替尼(40mg/d)或厄洛替尼(150mg/d)治療直到疾病進展。主要終點。PFS;關鍵的次要終點:OS.其他終點:客觀緩解率(ORR),疾病控制率(DCR),患者報告的結局,安全性。
結果:相比于接受厄洛替尼(n=397)治療,阿法替尼組(n=398)的OS明顯更好,可降低19%的死亡風險(中位OS:7.9 vs 6.8個月;HR,0.81;95%CI,0.69-095;p=0.008)。在6個月(63.6 vs 54.6%;p=0.010)、12個月(36.4 vs 28.2%;p=0.016)和18個月(22.0 vs 14.4%;p=0.013)可以看到OS的明顯差異。阿法替尼的PFS(2.6 vs 1.9個月;HR,0.81;95%CI,0.69-0.96;p=0.010)、ORR(5.5 vs 2.8%;p=0.055)和DCR(50.5 vs 39.5%;p=0.002)也明顯更優(yōu)。
阿法替尼組有更多的患者出現(xiàn)整體健康狀況/質量(35.7 vs 28.3%;p=0.041)、咳嗽(43.4 vs 35.2%;p=0.029)和呼吸困難(51.3 vs 44.1%;p=0.061)等癥狀的改善。兩組的不良反應發(fā)生情況具有可比性(三級及以上的不良反應,A vs E:57.1% vs 57.5%)。阿法替尼組的藥物相關3/4級腹瀉(9.9/0.5 vs 2.3/0.3%)、3級口腔炎(4.1 vs 0%)的發(fā)生率更高。厄洛替尼組的3級皮疹/痤瘡的發(fā)生率更高(5.9 vs 10.4%)。
結論:對于肺鱗癌患者的二線治療,阿法替尼相比厄洛替尼能明顯改善OS,PFS和DCR也明顯更好。此外,LL8研究中可以看到阿法替尼的不良反應可控,還可帶來生活質量的獲益以及癥狀控制,對于該類患者,阿法替尼應該更優(yōu)于厄洛替尼。臨床試驗信息:NCT01523587
閱讀摘要原文
Afatinib (A) vs erlotinib (E) as second-line therapy of patients (pts) with advanced squamous cell carcinoma (SCC) of the lung following platinum-based chemotherapy: Overall survival (OS) **ysis from the global phase III trial LUX-Lung 8 (LL8)。(Abstract No:8002)Author(s): Jean-Charles Soria, Enriqueta Felip, Manuel Cobo, et alSession Type: Oral Abstract Session
Background: Treatment options for pts with advanced SCC of the lung progressing after platinum-based chemotherapy are limited. Overexpression of EGFR, ErbB receptors and the dysregulation of their downstream pathways are implicated in SCC pathobiology. Primary **ysis of LL8 (2nd line A, an irreversible ErbB family blocker vs E, a reversible EGFR tyrosine kinase inhibitor [TKI; only TKI approved in this setting], in pts with SCC of the lung) showed significantly better progression-free survival (PFS) with A. OS and updated PFS are reported here.
Methods: Pts with stage IIIB/IV disease were randomized 1:1 to receive A (40 mg/day) or E (150 mg/day) until disease progression. Primary endpoint: PFS; key secondary endpoint: OS. Other endpoints: objective response (ORR), disease control (DCR), patient reported outcomes and safety. 632 events and a sample size of 800 pts was needed to detect a HR of 0.8 with 80% power for OS.
Results: OS was significantly better with A (n = 398) vs E (n = 397), with a 19% reduced risk of death (median 7.9 vs 6.8 mos; HR [95% CI] 0.81 [0.69–0.95]; p = 0.008)。 Significant differences in OS were seen at 6 (63.6 vs 54.6%; p = 0.010), 12 (36.4 vs 28.2%; p = 0.016) and 18 (22.0 vs 14.4%; p = 0.013) mos. PFS (median 2.6 vs 1.9 mos; HR [95% CI] 0.81 [0.69–0.96]; p = 0.010), ORR (5.5 vs 2.8%; p = 0.055) and DCR (50.5 vs 39.5%; p = 0.002) were all better for A vs E. More pts had improved global health status/quality of life (35.7 vs 28.3%; p = 0.041), cough (43.4 vs 35.2%; p = 0.029) and dyspnea (51.3 vs 44.1%; p = 0.061) with A vs E. Adverse event (AE) profiles were comparable (G ≥ 3 AEs: 57.1 and 57.5% for A vs E) with a higher incidence of drug-related G3/4 diarrhea (9.9/0.5 vs 2.3/0.3%), G3 stomatitis (4.1 vs 0%) with A and a higher incidence of G3 rash/acne with E (5.9 vs 10.4%)。 Preliminary data from FoundationOne **ysis of tumor blocks will be shown.
Conclusions: A significantly improved OS vs E in pts with SCC of the lung in a 2nd line setting. PFS and DCR were also significantly better. With a manageable AE profile, added QoL benefit, and symptom control seen in LL8, A should be preferred over E for these pts. Clinical trial ***rmation: NCT01523587
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