Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer

H. Borghaei, L. Paz-Ares, L. Horn, D. R. Spigel, M. Steins, N. E. Ready, L. Q. Chow, E. E. Vokes, E. Felip, E. Holgado, F. Barlesi, M. Kohlhufl, O. Arrieta, M. A. Burgio, J. Fayette, H. Lena, E. Poddubskaya, D. E. Gerber, S. N. Gettinger, C. M. Rudin & 8 others N. Rizvi, L. Crina, G. R. Blumenschein, S. J. Antonia, C. Dorange, C. T. Harbison, F. Graf Finckenstein, J. R. Brahmer

Research output: Contribution to journalArticle

3325 Citations (Scopus)

Abstract

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 followup, 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.).

Original languageEnglish (US)
Pages (from-to)1627-1639
Number of pages13
JournalNew England Journal of Medicine
Volume373
Issue number17
DOIs
StatePublished - Oct 22 2015

Fingerprint

docetaxel
Non-Small Cell Lung Carcinoma
Confidence Intervals
Survival
Platinum
Disease-Free Survival
nivolumab
Survival Rate

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Borghaei, H., Paz-Ares, L., Horn, L., Spigel, D. R., Steins, M., Ready, N. E., ... Brahmer, J. R. (2015). Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer. New England Journal of Medicine, 373(17), 1627-1639. https://doi.org/10.1056/NEJMoa1507643

Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer. / Borghaei, H.; Paz-Ares, L.; Horn, L.; Spigel, D. R.; Steins, M.; Ready, N. E.; Chow, L. Q.; Vokes, E. E.; Felip, E.; Holgado, E.; Barlesi, F.; Kohlhufl, M.; Arrieta, O.; Burgio, M. A.; Fayette, J.; Lena, H.; Poddubskaya, E.; Gerber, D. E.; Gettinger, S. N.; Rudin, C. M.; Rizvi, N.; Crina, L.; Blumenschein, G. R.; Antonia, S. J.; Dorange, C.; Harbison, C. T.; Graf Finckenstein, F.; Brahmer, J. R.

In: New England Journal of Medicine, Vol. 373, No. 17, 22.10.2015, p. 1627-1639.

Research output: Contribution to journalArticle

Borghaei, H, Paz-Ares, L, Horn, L, Spigel, DR, Steins, M, Ready, NE, Chow, LQ, Vokes, EE, Felip, E, Holgado, E, Barlesi, F, Kohlhufl, M, Arrieta, O, Burgio, MA, Fayette, J, Lena, H, Poddubskaya, E, Gerber, DE, Gettinger, SN, Rudin, CM, Rizvi, N, Crina, L, Blumenschein, GR, Antonia, SJ, Dorange, C, Harbison, CT, Graf Finckenstein, F & Brahmer, JR 2015, 'Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer', New England Journal of Medicine, vol. 373, no. 17, pp. 1627-1639. https://doi.org/10.1056/NEJMoa1507643
Borghaei H, Paz-Ares L, Horn L, Spigel DR, Steins M, Ready NE et al. Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer. New England Journal of Medicine. 2015 Oct 22;373(17):1627-1639. https://doi.org/10.1056/NEJMoa1507643
Borghaei, H. ; Paz-Ares, L. ; Horn, L. ; Spigel, D. R. ; Steins, M. ; Ready, N. E. ; Chow, L. Q. ; Vokes, E. E. ; Felip, E. ; Holgado, E. ; Barlesi, F. ; Kohlhufl, M. ; Arrieta, O. ; Burgio, M. A. ; Fayette, J. ; Lena, H. ; Poddubskaya, E. ; Gerber, D. E. ; Gettinger, S. N. ; Rudin, C. M. ; Rizvi, N. ; Crina, L. ; Blumenschein, G. R. ; Antonia, S. J. ; Dorange, C. ; Harbison, C. T. ; Graf Finckenstein, F. ; Brahmer, J. R. / Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer. In: New England Journal of Medicine. 2015 ; Vol. 373, No. 17. pp. 1627-1639.
@article{9aa2560d45d94244934eace0a702a04b,
title = "Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer",
abstract = "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 followup, 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.).",
author = "H. Borghaei and L. Paz-Ares and L. Horn and Spigel, {D. R.} and M. Steins and Ready, {N. E.} and Chow, {L. Q.} and Vokes, {E. E.} and E. Felip and E. Holgado and F. Barlesi and M. Kohlhufl and O. Arrieta and Burgio, {M. A.} and J. Fayette and H. Lena and E. Poddubskaya and Gerber, {D. E.} and Gettinger, {S. N.} and Rudin, {C. M.} and N. Rizvi and L. Crina and Blumenschein, {G. R.} and Antonia, {S. J.} and C. Dorange and Harbison, {C. T.} and {Graf Finckenstein}, F. and Brahmer, {J. R.}",
year = "2015",
month = "10",
day = "22",
doi = "10.1056/NEJMoa1507643",
language = "English (US)",
volume = "373",
pages = "1627--1639",
journal = "New England Journal of Medicine",
issn = "0028-4793",
publisher = "Massachussetts Medical Society",
number = "17",

}

TY - JOUR

T1 - Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer

AU - Borghaei, H.

AU - Paz-Ares, L.

AU - Horn, L.

AU - Spigel, D. R.

AU - Steins, M.

AU - Ready, N. E.

AU - Chow, L. Q.

AU - Vokes, E. E.

AU - Felip, E.

AU - Holgado, E.

AU - Barlesi, F.

AU - Kohlhufl, M.

AU - Arrieta, O.

AU - Burgio, M. A.

AU - Fayette, J.

AU - Lena, H.

AU - Poddubskaya, E.

AU - Gerber, D. E.

AU - Gettinger, S. N.

AU - Rudin, C. M.

AU - Rizvi, N.

AU - Crina, L.

AU - Blumenschein, G. R.

AU - Antonia, S. J.

AU - Dorange, C.

AU - Harbison, C. T.

AU - Graf Finckenstein, F.

AU - Brahmer, J. R.

PY - 2015/10/22

Y1 - 2015/10/22

N2 - 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 followup, 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.).

AB - 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 followup, 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.).

UR - http://www.scopus.com/inward/record.url?scp=84944937210&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84944937210&partnerID=8YFLogxK

U2 - 10.1056/NEJMoa1507643

DO - 10.1056/NEJMoa1507643

M3 - Article

VL - 373

SP - 1627

EP - 1639

JO - New England Journal of Medicine

JF - New England Journal of Medicine

SN - 0028-4793

IS - 17

ER -