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

被引：7762

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

共 20 条

[1] Nivolumab versus Docetaxel in Advanced Squamous-Cell Non-Small-Cell Lung Cancer [J].

Brahmer, Julie ;

Reckamp, Karen L. ;

Baas, Paul ;

Crino, Lucio ;

Eberhardt, Wilfried E. E. ;

Poddubskaya, Elena ;

Antonia, Scott ;

Pluzanski, Adam ;

Vokes, Everett E. ;

Holgado, Esther ;

Waterhouse, David ;

Ready, Neal ;

Gainor, Justin ;

Aren Frontera, Osvaldo ;

Havel, Libor ;

Steins, Martin ;

Garassino, Marina C. ;

Aerts, Joachim G. ;

Domine, Manuel ;

Paz-Ares, Luis ;

Reck, Martin ;

Baudelet, Christine ;

Harbison, Christopher T. ;

Lestini, Brian ;

Spigel, David R. .

NEW ENGLAND JOURNAL OF MEDICINE, 2015, 373 (02) :123-135

[2] Phase I Study of Single-Agent Anti-Programmed Death-1 (MDX-1106) in Refractory Solid Tumors: Safety, Clinical Activity, Pharmacodynamics, and Immunologic Correlates [J].

Brahmer, Julie R. ;

Drake, Charles G. ;

Wollner, Ira ;

Powderly, John D. ;

Picus, Joel ;

Sharfman, William H. ;

Stankevich, Elizabeth ;

Pons, Alice ;

Salay, Theresa M. ;

McMiller, Tracee L. ;

Gilson, Marta M. ;

Wang, Changyu ;

Selby, Mark ;

Taube, Janis M. ;

Anders, Robert ;

Chen, Lieping ;

Korman, Alan J. ;

Pardoll, Drew M. ;

Lowy, Israel ;

Topalian, Suzanne L. .

JOURNAL OF CLINICAL ONCOLOGY, 2010, 28 (19) :3167-3175

[3] Exomics and immunogenics Bridging mutational load and immune checkpoints efficacy [J].

Champiat, Stephane ;

Ferte, Charles ;

Lebel-Binay, Sophie ;

Eggermont, Alexander ;

Soria, Jean-Charles .

ONCOIMMUNOLOGY, 2014, 3 (01)

[4] New response evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1) [J].

Eisenhauer, E. A. ;

Therasse, P. ;

Bogaerts, J. ;

Schwartz, L. H. ;

Sargent, D. ;

Ford, R. ;

Dancey, J. ;

Arbuck, S. ;

Gwyther, S. ;

Mooney, M. ;

Rubinstein, L. ;

Shankar, L. ;

Dodd, L. ;

Kaplan, R. ;

Lacombe, D. ;

Verweij, J. .

EUROPEAN JOURNAL OF CANCER, 2009, 45 (02) :228-247

[5] Randomized phase III trial of docetaxel versus vinorelbine or ifosfamide in patients with advanced non-small-cell lung cancer previously treated with platinum-containing chemotherapy regimens [J].

Fossella, FV ;

DeVore, R ;

Kerr, RN ;

Crawford, J ;

Natale, RR ;

Dunphy, F ;

Kalman, L ;

Miller, V ;

Lee, JS ;

Moore, M ;

Gandara, D ;

Karp, D ;

Vokes, E ;

Kris, M ;

Kim, Y ;

Gamza, F ;

Hammershaimb, L .

JOURNAL OF CLINICAL ONCOLOGY, 2000, 18 (12) :2354-2362

[6] Erlotinib versus docetaxel as second-line treatment of patients with advanced non-small-cell lung cancer and wild-type EGFR tumours (TAILOR): a randomised controlled trial [J].

Garassino, Marina Chiara ;

Martelli, Olga ;

Broggini, Massimo ;

Farina, Gabriella ;

Veronese, Silvio ;

Rulli, Eliana ;

Bianchi, Filippo ;

Bettini, Anna ;

Longo, Flavia ;

Moscetti, Luca ;

Tomirotti, Maurizio ;

Marabese, Mirko ;

Ganzinelli, Monica ;

Lauricella, Calogero ;

Labianca, Roberto ;

Floriani, Irene ;

Giaccone, Giuseppe ;

Torri, Valter ;

Scanni, Alberto ;

Marsoni, Silvia .

LANCET ONCOLOGY, 2013, 14 (10) :981-988

[7] Pembrolizumab for the Treatment of Non-Small-Cell Lung Cancer [J].

Garon, Edward B. ;

Rizvi, Naiyer A. ;

Hui, Rina ;

Leighl, Natasha ;

Balmanoukian, Ani S. ;

Eder, Joseph Paul ;

Patnaik, Amita ;

Aggarwal, Charu ;

Gubens, Matthew ;

Horn, Leora ;

Carcereny, Enric ;

Ahn, Myung-Ju ;

Felip, Enriqueta ;

Lee, Jong-Seok ;

Hellmann, Matthew D. ;

Hamid, Omid ;

Goldman, Jonathan W. ;

Soria, Jean-Charles ;

Dolled-Filhart, Marisa ;

Rutledge, Ruth Z. ;

Zhang, Jin ;

Lunceford, Jared K. ;

Rangwala, Reshma ;

Lubiniecki, Gregory M. ;

Roach, Charlotte ;

Emancipator, Kenneth ;

Gandhi, Leena .

NEW ENGLAND JOURNAL OF MEDICINE, 2015, 372 (21) :2018-2028

[8] Ramucirumab plus docetaxel versus placebo plus docetaxel for second-line treatment of stage IV non-small-cell lung cancer after disease progression on platinum-based therapy (REVEL): a multicentre, double-blind, randomised phase 3 trial [J].

Garon, Edward B. ;

Ciuleanu, Tudor-Eliade ;

Arrieta, Oscar ;

Prabhash, Kumar ;

Syrigos, Konstantinos N. ;

Goksel, Tuncay ;

Park, Keunchil ;

Gorbunova, Vera ;

Dario Kowalyszyn, Ruben ;

Pikiel, Joanna ;

Czyzewicz, Grzegorz ;

Orlov, Sergey V. ;

Lewanski, Conrad R. ;

Thomas, Michael ;

Bidoli, Paolo ;

Dakhil, Shaker ;

Gans, Steven ;

Kim, Joo-Hang ;

Grigorescu, Alexandru ;

Karaseva, Nina ;

Reck, Martin ;

Cappuzzo, Federico ;

Alexandris, Ekaterine ;

Sashegyi, Andreas ;

Yurasov, Sergey ;

Perol, Maurice .

LANCET, 2014, 384 (9944) :665-673

[9] Overall Survival and Long-Term Safety of Nivolumab (Anti-Programmed Death 1 Antibody, BMS-936558, ONO-4538) in Patients With Previously Treated Advanced Non-Small-Cell Lung Cancer [J].

Gettinger, Scott N. ;

Horn, Leora ;

Gandhi, Leena ;

Spigel, David R. ;

Antonia, Scott J. ;

Rizvi, Naiyer A. ;

Powderly, John D. ;

Heist, Rebecca S. ;

Carvajal, Richard D. ;

Jackman, David M. ;

Sequist, Lecia V. ;

Smith, David C. ;

Leming, Philip ;

Carbone, David P. ;

Pinder-Schenck, Mary C. ;

Topalian, Suzanne L. ;

Hodi, F. Stephen ;

Sosman, Jeffrey A. ;

Sznol, Mario ;

McDermott, David F. ;

Pardoll, Drew M. ;

Sankar, Vindira ;

Ahlers, Christoph M. ;

Salvati, Mark ;

Wigginton, Jon M. ;

Hellmann, Matthew D. ;

Kollia, Georgia D. ;

Gupta, Ashok K. ;

Brahmer, Julie R. .

JOURNAL OF CLINICAL ONCOLOGY, 2015, 33 (18) :2004-U32

[10] Randomized phase III trial of pemetrexed versus docetaxel in patients with non-small-cell lung cancer previously treated with chemotherapy [J].

Hanna, N ;

Shepherd, FA ;

Fossella, FV ;

Pereira, JR ;

De Marinis, F ;

von Pawel, J ;

Gatzemeier, U ;

Tsao, TCY ;

Pless, M ;

Muller, T ;

Lim, HL ;

Desch, C ;

Szondy, K ;

Gervais, R ;

Shaharyar ;

Manegold, C ;

Paul, S ;

Paoletti, P ;

Einhorn, L ;

Bunn, PA .

JOURNAL OF CLINICAL ONCOLOGY, 2004, 22 (09) :1589-1597

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