Nivolumab versus Docetaxel in Advanced Nonsquamous Non-Small-Cell Lung Cancer

被引：7846

作者：

Borghaei, H. ^{[1
]}

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

Horn, L. ^{[6
]}

Spigel, D. R. ^{[7
,8
]}

Steins, M. ^{[9
]}

Ready, N. E. ^{[11
]}

Chow, L. Q. ^{[12
]}

Vokes, E. E. ^{[13
]}

Felip, E. ^{[3
,4
]}

Holgado, E. ^{[5
]}

Barlesi, F. ^{[14
]}

Kohlhaeufl, M. ^{[10
]}

Arrieta, O. ^{[17
]}

Burgio, M. A. ^{[18
]}

Fayette, J. ^{[15
]}

Lena, H. ^{[16
]}

Poddubskaya, E. ^{[20
]}

Gerber, D. E. ^{[21
]}

Gettinger, S. N. ^{[22
]}

Rudin, C. M. ^{[23
]}

Rizvi, N. ^{[23
]}

Crino, L. ^{[19
]}

Blumenschein, G. R. ^{[24
]}

Antonia, S. J. ^{[25
]}

Dorange, C. ^{[26
]}

Harbison, C. T. ^{[26
]}

Finckenstein, F. Graf ^{[26
]}

Brahmer, J. R. ^{[27
]}

机构：

[1] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA

[2] Hosp Univ Virgen del Rocio, Seville, Spain

[3] Vall dHebron Univ Hosp, Barcelona, Spain

[4] Vall dHebron Inst Oncol, Barcelona, Spain

[5] Hosp Madrid, Madrid, Spain

[6] Vanderbilt Ingram Canc Ctr, Nashville, TN USA

[7] Sarah Cannon Res Inst, Nashville, TN USA

[8] Tennessee Oncol, Nashville, TN USA

[9] Univ Heidelberg Hosp, Thoraxklin, Heidelberg, Germany

[10] Robert Bosch Krankenhaus Stuttgart, Gerlingen, Germany

[11] Duke Univ, Med Ctr, Durham, NC USA

[12] Univ Washington, Seattle, WA 98195 USA

[13] Univ Chicago Med & Biol Sci, Chicago, IL USA

[14] Aix Marseille Univ, Assistance Publ Hop Marseille, Marseille, France

[15] Ctr Leon Berard, F-69373 Lyon, France

[16] Ctr Hosp Univ Rennes, Rennes, France

[17] Inst Nacl Cancerol, Mexico City, DF, Mexico

[18] Ist Sci Romagnolo Studio Cura Tumori IRCCS, Meldola, Forli Cesena, Italy

[19] Osped Perugia, Perugia, Italy

[20] NN Blokhin Russian Canc Res Ctr, Moscow, Russia

[21] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA

[22] Yale Comprehens Canc Ctr, New Haven, CT USA

[23] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA

[24] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA

[25] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA

[26] Bristol Myers Squibb Co, Princeton, NJ USA

[27] Johns Hopkins, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA

来源：

NEW ENGLAND JOURNAL OF MEDICINE | 2015年 / 373卷 / 17期

关键词：

PHASE-III TRIAL; ANTI-PD-1; ANTIBODY; SAFETY; ERLOTINIB; BLOCKADE;

D O I：

10.1056/NEJMoa1507643

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

BACKGROUND Nivolumab, a fully human IgG4 programmed death 1 (PD-1) immune-checkpoint-inhibitor antibody, disrupts PD-1-mediated signaling and may restore antitumor immunity. METHODS In this randomized, open-label, international phase 3 study, we assigned patients with nonsquamous non-small-cell lung cancer (NSCLC) that had progressed during or after platinum-based doublet chemotherapy to receive nivolumab at a dose of 3 mg per kilogram of body weight every 2 weeks or docetaxel at a dose of 75 mg per square meter of body-surface area every 3 weeks. The primary end point was overall survival. RESULTS Overall survival was longer with nivolumab than with docetaxel. The median overall survival was 12.2 months (95% confidence interval [CI], 9.7 to 15.0) among 292 patients in the nivolumab group and 9.4 months (95% CI, 8.1 to 10.7) among 290 patients in the docetaxel group (hazard ratio for death, 0.73; 96% CI, 0.59 to 0.89; P = 0.002). At 1 year, the overall survival rate was 51% (95% CI, 45 to 56) with nivolumab versus 39% (95% CI, 33 to 45) with docetaxel. With additional follow-up, the overall survival rate at 18 months was 39% (95% CI, 34 to 45) with nivolumab versus 23% (95% CI, 19 to 28) with docetaxel. The response rate was 19% with nivolumab versus 12% with docetaxel (P = 0.02). Although progression-free survival did not favor nivolumab over docetaxel (median, 2.3 months and 4.2 months, respectively), the rate of progression-free survival at 1 year was higher with nivolumab than with docetaxel (19% and 8%, respectively). Nivolumab was associated with even greater efficacy than docetaxel across all end points in subgroups defined according to prespecified levels of tumor-membrane expression (>= 1%, >= 5%, and >= 10%) of the PD-1 ligand. Treatment-related adverse events of grade 3 or 4 were reported in 10% of the patients in the nivolumab group, as compared with 54% of those in the docetaxel group. CONCLUSIONS Among patients with advanced nonsquamous NSCLC that had progressed during or after platinum-based chemotherapy, overall survival was longer with nivolumab than with docetaxel. (Funded by Bristol-Myers Squibb; CheckMate 057 ClinicalTrials.gov number, NCT01673867.)

引用

页码：1627 / 1639

页数：13

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