VP3-2022: Pembrolizumab (pembro) versus placebo for early-stage non-small cell lung cancer (NSCLC) following complete resection and adjuvant chemotherapy (chemo) when indicated: Randomized, triple-blind, phase III EORTC-1416-LCG/ETOP 8-15 e PEARLS/KEYNOTE-091 study

被引：58

作者：

Paz-Ares, L. ^{[1
,2
]}

O'Brien, M. E. R. ^{[3
]}

Mauer, M. ^{[2
,4
]}

Dafni, U. ^{[3
,5
,6
]}

Oselin, K. ^{[4
,7
]}

Havel, L. ^{[5
,8
,9
]}

Gonzalez, E. Esteban ^{[6
,10
]}

Isla, D. ^{[7
,11
]}

Martinez-Marti, A. ^{[8
,12
]}

Faehling, M. ^{[10
]}

Tsuboi, M. ^{[11
]}

Lee, J-s. ^{[12
]}

Nakagawa, K. ^{[2
,13
]}

Yang, J. ^{[3
,14
]}

Keller, S. M. ^{[4
,15
]}

Jha, N. ^{[2
,4
]}

Marreaud, S. I. ^{[5
,16
]}

Stahel, R. A. ^{[6
,17
]}

Peters, S. ^{[18
]}

Besse, B. ^{[19
]}

机构：

[1] Hosp Univ 12 Octubre, Med Oncol, CNIO, Madrid, Spain

[2] Royal Marsden Hosp, Med Oncol, London, England

[3] Stat European Org Res & Treatment Canc, Brussels, Belgium

[4] Natl & Kapodistrian Univ Athens, ETOP Stat Ctr, Athens, Greece

[5] North Estonia Med Ctr, Med Oncol, Tallinn, Estonia

[6] Charles Univ Prague, Pulm Med, Prague, Czech Republic

[7] Hosp Univ Cent Asturias, Med Oncol, Oviedo, Spain

[8] Univ Hosp Lozano Blesa, Med Oncol, IIS Aragon, Zaragoza, Spain

[9] Vall Hebron Univ Hosp, Vall Hebron Inst Oncol VHIO, Med Oncol, Barcelona, Spain

[10] Natl Canc Ctr Hosp East, Thorac Surg & Oncol, Kashiwa, Japan

[11] Klinikum Esslingen, Klin Kardiol & Pneumol, Esslingen, Germany

[12] Seoul Natl Univ, Coll Med, Internal Med, Bundang Hosp, Seongnam, South Korea

[13] Kindai Univ Med, Med, Main Campus, Osaka, Japan

[14] Merck & Co Inc, Biostat & Res Decis Sci, Kenilworth, NJ USA

[15] Merck & Co Inc, Global Clin Dev, Kenilworth, NJ USA

[16] European Org Res Treatment Canc, Med, Brussels, Belgium

[17] European Thorac Oncol Platform ETOP, Med Oncol & Hematol, Bern, Switzerland

[18] Lausanne Univ Hosp, Oncol Dept, Lausanne, Switzerland

[19] Inst Gustave Roussy, Thorac Oncol, Villejuif, France

来源：

ANNALS OF ONCOLOGY | 2022年 / 33卷 / 04期

关键词：

D O I：

10.1016/j.annonc.2022.02.224

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

BACKGROUND Pembro is a standard of care for advanced NSCLC. PEARLS/ KEYNOTE-091 (NCT02504372) evaluated adjuvant pembro vs placebo for patients (pts) with completely resected early-stage NSCLC. METHODS Eligible pts with completely resected stage IB (T > 4 cm), II, or IIIA NSCLC per AJCC v7 followed by adjuvant chemo as indicated per guidelines, ECOG PS 0-1, and any PD-L1 expression were randomized 1:1 to pembro 200 mg or placebo Q3W for 18 doses (w1 year). Dual primary end points are DFS in the all-comers and PD-L1 TPS > 50% populations. Secondary end points are DFS in the TPS > 1% population, OS in the all-comers, TPS > 50% and > 1% populations, and safety. Data are from the protocol-specified second interim analysis (IA2; 20 September 2021, data cutoff). RESULTS 1177 pts were randomized to pembro (N = 590) or placebo (N = 587), including 168 and 165, respectively, who had TPS >= 50%. Baseline characteristics were generally balanced between arms. Median time from randomization to data cutoff for IA2 was 35.6 mo (range 16.5-68.0). DFS was significantly improved with pembro in the all-comers population (median 53.6 vs 42.0 mo; HR 0.76; 95% CI 0.63-0.91; P = 0.0014); the significance boundary was not crossed for the TPS >= 50% population (median not reached in either arm; HR 0.82; 95% CI 0.57-1.18; P = 0.14). With only 209 events, the significance boundary for OS in the all-comers population was not crossed (18-mo rate 91.7% vs 91.3%; HR 0.87; 95% CI 0.67-1.15; P = 0.17). Median number of doses was 17 for pembro vs 18 for placebo. AEs were grade >= 3 in 34.1% of pts in the pembro arm vs 25.8% in the placebo arm and led to discontinuation in 19.8% vs 5.9%; treatment-related AEs led to death in 0.7% vs 0%. CONCLUSIONS Adjuvant pembro provided a statistically significant, clini-cally meaningful DFS improvement following complete resection and, when indicated, adjuvant chemo in pts with stage IB (T >= 4 cm)-IIIA NSCLC, regardless of PD-L1 expression. The pembro safety profile was as expected. DFS in the PD-L1-defined populations and OS will be tested at future analyses according to the analysis plan.

引用

页码：451 / 453

页数：3