Nivolumab plus ipilimumab versus chemotherapy as first-line treatment in advanced non-small-cell lung cancer with high tumour mutational burden: patient-reported outcomes results from the randomised, open-label, phase III CheckMate 227 trial

被引：165

作者：

Reck, Martin ^{[1
]}

Schenker, Michael ^{[2
]}

Lee, Ki Hyeong ^{[3
]}

Provencio, Mariano ^{[4
]}

Nishio, Makoto ^{[5
]}

Lesniewski-Kmak, Krzysztof ^{[6
]}

Sangha, Randeep ^{[7
]}

Ahmed, Samreen ^{[8
]}

Raimbourg, Judith ^{[9
]}

Feeney, Kynan ^{[10
,11
]}

Corre, Romain ^{[12
]}

Franke, Fabio Andre ^{[13
]}

Richardet, Eduardo ^{[14
]}

Penrod, John R. ^{[15
]}

Yuan, Yong ^{[15
]}

Nathan, Faith E. ^{[15
]}

Bhagavatheeswaran, Prabhu ^{[15
]}

DeRosa, Michael ^{[16
]}

Taylor, Fiona ^{[16
]}

Lawrance, Rachael ^{[17
]}

Brahmer, Julie ^{[18
]}

机构：

[1] German Ctr Lung Res DZL, ARCN, LungenClin Grosshansdorf, Wohrendamm 80, D-22927 Grosshansdorf, Germany

[2] Cent Oncol Sf Nectarie, 23A Caracal St, Craiova 200347, Romania

[3] Chungbuk Natl Univ Hosp, 776,1 Sunhwan Ro, Cheongju 28644, Chungcheonbuk D, South Korea

[4] Univ Autonoma Madrid, Inst Invest Puerta Hierro, Hosp Puerta Hierro de Majadahonda, C Manuel de Falla 1, Madrid 28222, Majadahonda, Spain

[5] Japanese Fdn Canc Res, Canc Inst Hosp, Koto Ku, 3-8-31 Ariake, Tokyo 1358550, Japan

[6] Gdansk Med Univ, Oddzial Onkol Radioterapii Szpital, UI Powstania Styczniowego 1, PL-81519 Gdynia, Poland

[7] Cross Canc Inst, 11560 Univ Ave, Edmonton, AB T6G 1Z2, Canada

[8] Univ Hosp Leicester NHS Trust, Dept Infect, Leicester LE1 5WW, Leics, England

[9] Inst Cancerol Ouest, Ctr Rene Gauducheau, Blvd Jacques Monad, F-44805 Nantes, France

[10] Notre Dame Univ, 100 Murdoch Dr, Perth, WA 6150, Australia

[11] Edith Cowan Univ, 100 Murdoch Dr, Perth, WA 6150, Australia

[12] CHU Rennes, 2 Rue Henri le Guilloux, F-35033 Rennes, France

[13] Hosp Caridade Ijui, CACON, Av David Jose Martins, BR-98700000 Ijui, RS, Brazil

[14] IONC Univ Catolica Cordoba, Parana 560 2 Piso, RA-5000 Cordoba, Argentina

[15] Bristol Myers Squibb Co, 3401 Princeton Pike, Lawrenceville, NJ 08648 USA

[16] Adelphi Values, 290 Congress St 7th Floor, Boston, MA 02210 USA

[17] Adelphi Values, Grimshaw Ln, Bollington SK10 5JB, Cheshire, England

[18] Johns Hopkins, Sidney Kimmel Comprehens Canc Ctr, 1650 Orleans St,CRB1-G94, Baltimore, MD 21287 USA

来源：

EUROPEAN JOURNAL OF CANCER | 2019年 / 116卷

关键词：

Antineoplastic agents; Carcinoma; Ipilimumab; Lung neoplasms; Nivolumab; Non-small-cell lung cancer; Platinum-doublet chemotherapy; Quality of life; Surveys and questionnaires; QUALITY-OF-LIFE; DOCETAXEL; SYMPTOMS; MULTICENTER;

D O I：

10.1016/j.ejca.2019.05.008

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Background: In the phase I I I CheckMate 227 study, first-line nivolumab + ipilimumab significantly prolonged progression-free survival (co-primary end-point) versus chemotherapy in patients with advanced nonesmall-cell lung cancer (NSCLC) and high tumour mutational burden (TMB; >= 10 mutations/megabase). Aim: To evaluate patient-reported outcomes (PROs) in this population. Methods: Disease-related symptoms and general health status were assessed using the validated PRO questionnaires Lung Cancer Symptom Scale (LCSS) and EQ-5D, respectively. LCSS average symptom burden index (ASBI) and three-item global index (3-IGI) and EQ-5D visual analogue scale (VAS) and utility index (UI) scores and changes from baseline were analysed descriptively. Longitudinal changes were assessed by mixed-effect model repeated measures (MMRMs) and time to first deterioration/improvement analyses. Results: In the high TMB population, PRO questionnaire completion rates were similar to 90% at baseline and >80% for most on-treatment assessments. During treatment, mean changes from baseline with nivolumab + ipilimumab showed early, clinically meaningful improvements in LCSS ASBI/3-IGI and EQ-5D VAS/UI; with chemotherapy, symptoms and health-related quality of life remained stable (LCSS ASBI/3-IGI, EQ-5D UI) or improved following induction (EQ-5D VAS). MMRM-assessed changes in symptom burden were improved with nivolumab + ipilimumab versus chemotherapy. Symptom deterioration by week 12 was lower with nivolumab + ipilimumab versus chemotherapy (22.3% versus 35.0%; absolute risk reduction: 12.7% [95% confidence interval 2.4-22.5]), irrespective of discontinuation. Time to first deterioration was delayed with nivolumab + ipilimumab versus chemotherapy across LCSS and EQ-5D summary measures. Conclusion: First-line nivolumab + ipilimumab demonstrated early, sustained improvements in PROs versus chemotherapy in patients with advanced NSCLC and high TMB. (C) 2019 The Authors. Published by Elsevier Ltd.

引用

页码：137 / 147

页数：11

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