背景:在 3 期隨機 CheckMate 9LA 試驗(NCT03215706)中,一線 NIVO + IPI 聯合2 周期化療與單藥化療 4 周期相比,顯著改延長了總生存期 (OS), 無進展生存期 (PFS)和客觀應答率 (ORR)。無論 PD-L1 表達水平和組織學分型如何,我們都觀察到臨床療效。我們將在此彙報至少 2 年的跟蹤隨訪數據。 Background: In the rando
背景:在 3 期隨機 CheckMate 9LA 試驗(NCT03215706)中,一線 NIVO + IPI 聯合2 周期化療與單藥化療 4 周期相比,顯著改延長了總生存期 (OS), 無進展生存期 (PFS)和客觀應答率 (ORR)。無論 PD-L1 表達水平和組織學分型如何,我們都觀察到臨床療效。我們將在此彙報至少 2 年的跟蹤隨訪數據。
Background: In the randomized phase 3 CheckMate 9LA trial (NCT03215706), first-line NIVO + IPI combined with 2 cycles of chemo significantly improved overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) vs chemo alone (4 cycles). Clinical benefit was observed regardless of programmed death ligand 1 (PD-L1) expression level and histology. Here we report data with 2 years’ minimum follow-up from this study.
方法:我們將 IV 期或複發 NSCLC、ECOG 評分≤1 分 和已知無明確 EGFR/ALK 突變的成人患者(pts)按 PD-L1(< 1% 與 ≥1%),性別,和組織學表型 (鱗癌 VS 非鱗癌)分層,並被 1:1 隨機分組到 NIVO 360 mg Q3W + IPI 1 mg / kg Q6W + 化療 (2 周期; n = 361) 或單藥化療 (4 周期; n = 358)。在化療組中非鱗 NSCLC 的 pts 可以接受培美曲塞維持。主要終點是 OS。次要終點包括通過獨立中心盲審的 PFS 和 ORR,以及 PD-L1 不同等級的療效。此研究的安全性是得以保證的。
Methods: Adult patients (pts) with stage IV / recurrent NSCLC, ECOG performance status ≤ 1, and no known sensitizing EGFR/ALK alterations were stratified by PD-L1 (< 1% vs ≥ 1%), sex, and histology (squamous vs non-squamous) and were randomized 1:1 to NIVO 360 mg Q3W + IPI 1 mg/kg Q6W + chemo (2 cycles; n = 361) or chemo alone (4 cycles; n = 358). Pts with non-squamous NSCLC in the chemo-alone arm could receive pemetrexed maintenance. The primary endpoint was OS. Secondary endpoints included PFS and ORR by blinded independent central review, and efficacy by different PD-L1 levels. Safety was exploratory.
結果:OS 至少隨訪 24.4 個月(數據庫於 2021 年 2 月 18 日鎖定),經 NIVO + IPI + chemo 治療的 pts 與單藥化療相比得到了 OS 獲益,中位 OS 分別為 15.8 個月與 11.0 個月(HR, 0.72 [95% CI, 0.61–0.86]);2 年 OS 率分別為 38%和 26%。經 NIVO + IPI + chemo 治療與單藥化療的中位 PFS 分別為 6.7 個月與 5.3 個月 (HR,0.67 [95% CI,0.56-0.79]);分別有 8%和 37%的有疾病進展的患者接受了後續免疫治療。NIVO+IPI+chemo ORR 38% VS 單藥化療 ORR 25%。在所有隨機分組的 pts 和大多數子分組都觀察到了類似於 NIVO+ IPI + chemo VS 單藥化療的臨床獲益,包括不同的 PD-L1 表達水平或組織學分型。與治療相關的任何等級和 3-4 級不良事件在 NIVO + IPI + chemo 組分別為 92% 和 48% VS 化療組為 88% 和 38%。
Results: At a minimum follow-up of 24.4 months for OS (database lock: Feb 18, 2021), pts treated with NIVO + IPI + chemo continued to derive OS benefit vs chemo, with a median OS of 15.8 months vs 11.0 months, respectively (HR, 0.72 [95% CI, 0.61–0.86]); 2-year OS rates were 38% vs 26%. Median PFS with NIVO + IPI + chemo vs chemo was 6.7 months vs 5.3 months (HR, 0.67 [95% CI, 0.56–0.79]); 8% and 37% of pts who had disease progression received subsequent immunotherapy, respectively. ORR was 38% with NIVO + IPI + chemo vs 25% with chemo. Similar clinical benefit with NIVO + IPI + chemo vs chemo was observed in all randomized pts and across the majority of subgroups, including by PD-L1 expression level (Table) or histology. Any grade and grade 3–4 treatment-related adverse events were reported in 92% and 48% of pts in the NIVO + IPI + chemo arm vs 88% and 38% in the chemo arm, respectively.
Summary of efficacy outcomes by PD-L1 expression. |
||||||||
PD-L1 |
PD-L1 |
PD-L1 |
PD-L1 |
PD-L1 |
PD-L1 |
All randomized |
All randomized |
|
NIVO + IPI + chemo |
Chemo |
NIVO + IPI +chemo |
Chemo |
NIVO + IPI +chemo |
Chemo |
NIVO + IPI +chemo |
Chemo |
|
Median OS, months |
17.7 |
9.8 |
15.8 |
10.9 |
18.9 |
12.9 |
15.8 |
11.0 |
OS HR (95% CI) |
0.67(0.51–0.88) |
- |
0.70(0.56–.89) |
- |
0.67(0.46–.97) |
- |
0.72(0.61–0.86) |
- |
2-year OS rate, % |
37 |
22 |
41 |
28 |
45 |
32 |
38 |
26 |
2-year PFS rate, % |
20 |
5 |
20 |
9 |
28 |
10 |
20 |
8 |
ORR, n (%) |
42 (31) |
26 (20) |
87 (43) |
57 (28) |
38 (50) |
31 (32) |
137 (38) |
91 (25) |
Median duration of response, months |
17.5 |
4.3 |
11.8 |
5.6 |
26.0 |
5.4 |
13.0 |
5.6 |
Responders with ongoing response |
45 |
0 |
33 |
13 |
52 |
16 |
34 |
12 |
結論:在晚期 Nsclc 的 pts 治療中,至少2年的隨訪、一線 NIVO + IPI + chemo 方案具有持久生存和臨床獲益;未發現新的安全信號。
Conclusion: With 2 years’ minimum follow-up, first-line NIVO + IPI + chemo demonstrated durable survival and benefit versus chemo in pts with advanced NSCLC; no new safety signals were identified.
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