Phase III Trial of Ipilimumab Combined With Paclitaxel and Carboplatin in Advanced Squamous Non-Small-Cell Lung Cancer

被引：318

作者：

Govindan, Ramaswamy ^{[1
]}

Szczesna, Aleksandra ^{[2
]}

Ahn, Myung-Ju ^{[4
]}

Schneider, Claus-Peter ^{[6
]}

Gonzalez Mella, Pablo Fernando ^{[9
,10
]}

Barlesi, Fabrice ^{[11
]}

Han, Baohui ^{[12
]}

Ganea, Doina Elena ^{[14
]}

Von Pawel, Joachim ^{[7
]}

Vladimirov, Vladimir ^{[15
]}

Fadeeva, Natalia ^{[16
]}

Lee, Ki Hyeong ^{[5
]}

Kurata, Takayasu ^{[17
]}

Zhang, Li ^{[13
]}

Tamura, Tomohide ^{[18
]}

Postmus, Pieter E. ^{[19
]}

Jassem, Jacek ^{[3
]}

O'Byrne, Kenneth ^{[20
,21
]}

Kopit, Justin ^{[22
]}

Li, Mingshun ^{[22
]}

Tschaika, Marina ^{[22
]}

Reck, Martin ^{[8
]}

机构：

[1] Washington Univ, Sch Med, St Louis, MO USA

[2] Mazowieckie Ctr Leczenia Chorob Pluc & Gruzlicy, Otwock, Poland

[3] Med Univ Gdansk, Gdansk, Poland

[4] Sungkyunkwan Univ, Samsung Med Ctr, Seoul, South Korea

[5] Chungbuk Natl Univ Hosp, Cheongju, South Korea

[6] Zentralklin Bad Berka, Bad Berka, Germany

[7] Asklepius Fachkliniken, Gauting, Germany

[8] German Ctr Lung Res, Airway Res Ctr North, LungenClin Grosshansdorf, Grosshansdorf, Germany

[9] Univ Valparaiso, Ctr Invest Clin, Santiago, Chile

[10] Fdn Arturo Lopez Perez, Santiago, Chile

[11] Aix Marseille Univ, AP HM, Marseille, France

[12] Shanghai Jiao Tong Univ, Shanghai Chest Hosp, Shanghai, Peoples R China

[13] Sun Yat Sen Univ, Canc Ctr, Guangzhou, Guangdong, Peoples R China

[14] Spitalul Judetean Urgenta Suceava, Sfantul Loan Cel Nou, Suceava, Romania

[15] Pyatigorsk Oncol Dispensary, State Healthcare Inst, Pyatigorsk, Russia

[16] Chelyabinsk Reg Oncol Dispensary, Chelyabinsk, Russia

[17] Kansai Med Univ, Hirakata Hosp, Osaka, Japan

[18] St Lukes Int Hosp, Tokyo, Japan

[19] Univ Liverpool, Liverpool, Merseyside, England

[20] Princess Alexandra Hosp, Brisbane, Qld, Australia

[21] Queensland Univ Technol, Brisbane, Qld, Australia

[22] Bristol Myers Squibb, Princeton, NJ USA

来源：

JOURNAL OF CLINICAL ONCOLOGY | 2017年 / 35卷 / 30期

关键词：

NIVOLUMAB PLUS IPILIMUMAB; CD8(+) T-CELLS; 1ST-LINE TREATMENT; OPEN-LABEL; CTLA-4; BLOCKADE; ADVANCED MELANOMA; NAIVE PATIENTS; MULTICENTER; INFILTRATION; CHEMOTHERAPY;

D O I：

10.1200/JCO.2016.71.7629

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Purpose Patients with squamous non-small-cell lung cancer (NSCLC) have poor prognosis and limited treatment options. This randomized, double-blind, phase III study investigated the efficacy and safety of first-line ipilimumab or placebo plus paclitaxel and carboplatin in advanced squamous NSCLC. Patients and Methods Patients with stage IV or recurrent chemotherapy-naive squamous NSCLC were randomly assigned (1: 1) to receive paclitaxel and carboplatin plus blinded ipilimumab 10 mg/kg or placebo every 3 weeks on a phased induction schedule comprising six chemotherapy cycles, with ipilimumab or placebo from cycles 3 to 6 and then, after induction treatment, ipilimumab or placebo maintenance every 12 weeks for patients with stable disease or better. The primary end point was overall survival (OS) in patients receiving at least one dose of blinded study therapy. Results Of 956 randomly assigned patients, 749 received at least one dose of blinded study therapy (chemotherapy plus ipilimumab, n = 388; chemotherapy plus placebo, n = 361). Median OS was 13.4 months for chemotherapy plus ipilimumab and 12.4 months for chemotherapy plus placebo (hazard ratio, 0.91; 95% CI, 0.77 to 1.07; P = .25). Median progression-free survival was 5.6 months for both groups (hazard ratio, 0.87; 95% CI, 0.75 to 1.01). Rates of grade 3 or 4 treatment-related adverse events (TRAEs), any-grade serious TRAEs, and TRAEs leading to discontinuation were numerically higher with chemotherapy plus ipilimumab (51%, 33%, and 28%, respectively) than with chemotherapy plus placebo (35%, 10%, and 7%, respectively). Seven treatment-related deaths occurred with chemotherapy plus ipilimumab, and one occurred with chemotherapy plus placebo. Conclusion The addition of ipilimumab to first-line chemotherapy did not prolong OS compared with chemotherapy alone in patients with advanced squamous NSCLC. The safety profile of chemotherapy plus ipilimumab was consistent with that observed in previous lung and melanoma studies. Ongoing studies are evaluating ipilimumab in combination with nivolumab in this population. (C) 2017 by American Society of Clinical Oncology

引用

页码：3449 / +

页数：11

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