Nivolumab versus docetaxel in previously treated advanced non-small-cell lung cancer (CheckMate 017 and CheckMate 057): 3-year update and outcomes in patients with liver metastases

E E Vokes, N Ready, E Felip, L Horn, M A Burgio, S J Antonia, O Arén Frontera, S Gettinger, E Holgado, D Spigel, D Waterhouse, M Domine, M Garassino, L Q M Chow, G Blumenschein, F Barlesi, B Coudert, J Gainor, O Arrieta, J BrahmerC Butts, M Steins, W J Geese, A Li, D Healey, L Crinò

Research output: Contribution to journalArticle

Abstract

Background: Long-term data with immune checkpoint inhibitors in non-small-cell lung cancer (NSCLC) are limited. Two phase III trials demonstrated improved overall survival (OS) and a favorable safety profile with the anti-programmed death-1 antibody nivolumab versus docetaxel in patients with previously treated advanced squamous (CheckMate 017) and nonsquamous (CheckMate 057) NSCLC. We report results from ≥3 years' follow-up, including subgroup analyses of patients with liver metastases, who historically have poorer prognosis among patients with NSCLC.

Patients and methods: Patients were randomized 1 : 1 to nivolumab (3 mg/kg every 2 weeks) or docetaxel (75 mg/m2 every 3 weeks) until progression or discontinuation. The primary end point of each study was OS. Patients with baseline liver metastases were pooled across studies by treatment for subgroup analyses.

Results: After 40.3 months' minimum follow-up in CheckMate 017 and 057, nivolumab continued to show an OS benefit versus docetaxel: estimated 3-year OS rates were 17% [95% confidence interval (CI), 14% to 21%] versus 8% (95% CI, 6% to 11%) in the pooled population with squamous or nonsquamous NSCLC. Nivolumab was generally well tolerated, with no new safety concerns identified. Of 854 randomized patients across both studies, 193 had baseline liver metastases. Nivolumab resulted in improved OS compared with docetaxel in patients with liver metastases (hazard ratio, 0.68; 95% CI, 0.50-0.91), consistent with findings from the overall pooled study population (hazard ratio, 0.70; 95% CI, 0.61-0.81). Rates of treatment-related hepatic adverse events (primarily grade 1-2 liver enzyme elevations) were slightly higher in nivolumab-treated patients with liver metastases (10%) than in the overall pooled population (6%).

Conclusions: After 3 years' minimum follow-up, nivolumab continued to demonstrate an OS benefit versus docetaxel in patients with advanced NSCLC. Similarly, nivolumab demonstrated an OS benefit versus docetaxel in patients with liver metastases, and remained well tolerated.

Clinical trial registration: CheckMate 017: NCT01642004; CheckMate 057: NCT01673867.

Original languageEnglish
Pages (from-to)959-965
Number of pages7
JournalAnnals of oncology : official journal of the European Society for Medical Oncology
Volume29
Issue number4
DOIs
Publication statusPublished - Apr 1 2018

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docetaxel
Non-Small Cell Lung Carcinoma
Neoplasm Metastasis
Liver
Survival
Confidence Intervals
nivolumab
Population
Safety

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Nivolumab versus docetaxel in previously treated advanced non-small-cell lung cancer (CheckMate 017 and CheckMate 057) : 3-year update and outcomes in patients with liver metastases. / Vokes, E E; Ready, N; Felip, E; Horn, L; Burgio, M A; Antonia, S J; Arén Frontera, O; Gettinger, S; Holgado, E; Spigel, D; Waterhouse, D; Domine, M; Garassino, M; Chow, L Q M; Blumenschein, G; Barlesi, F; Coudert, B; Gainor, J; Arrieta, O; Brahmer, J; Butts, C; Steins, M; Geese, W J; Li, A; Healey, D; Crinò, L.

In: Annals of oncology : official journal of the European Society for Medical Oncology, Vol. 29, No. 4, 01.04.2018, p. 959-965.

Research output: Contribution to journalArticle

Vokes, EE, Ready, N, Felip, E, Horn, L, Burgio, MA, Antonia, SJ, Arén Frontera, O, Gettinger, S, Holgado, E, Spigel, D, Waterhouse, D, Domine, M, Garassino, M, Chow, LQM, Blumenschein, G, Barlesi, F, Coudert, B, Gainor, J, Arrieta, O, Brahmer, J, Butts, C, Steins, M, Geese, WJ, Li, A, Healey, D & Crinò, L 2018, 'Nivolumab versus docetaxel in previously treated advanced non-small-cell lung cancer (CheckMate 017 and CheckMate 057): 3-year update and outcomes in patients with liver metastases', Annals of oncology : official journal of the European Society for Medical Oncology, vol. 29, no. 4, pp. 959-965. https://doi.org/10.1093/annonc/mdy041
Vokes, E E ; Ready, N ; Felip, E ; Horn, L ; Burgio, M A ; Antonia, S J ; Arén Frontera, O ; Gettinger, S ; Holgado, E ; Spigel, D ; Waterhouse, D ; Domine, M ; Garassino, M ; Chow, L Q M ; Blumenschein, G ; Barlesi, F ; Coudert, B ; Gainor, J ; Arrieta, O ; Brahmer, J ; Butts, C ; Steins, M ; Geese, W J ; Li, A ; Healey, D ; Crinò, L. / Nivolumab versus docetaxel in previously treated advanced non-small-cell lung cancer (CheckMate 017 and CheckMate 057) : 3-year update and outcomes in patients with liver metastases. In: Annals of oncology : official journal of the European Society for Medical Oncology. 2018 ; Vol. 29, No. 4. pp. 959-965.
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title = "Nivolumab versus docetaxel in previously treated advanced non-small-cell lung cancer (CheckMate 017 and CheckMate 057): 3-year update and outcomes in patients with liver metastases",
abstract = "Background: Long-term data with immune checkpoint inhibitors in non-small-cell lung cancer (NSCLC) are limited. Two phase III trials demonstrated improved overall survival (OS) and a favorable safety profile with the anti-programmed death-1 antibody nivolumab versus docetaxel in patients with previously treated advanced squamous (CheckMate 017) and nonsquamous (CheckMate 057) NSCLC. We report results from ≥3 years' follow-up, including subgroup analyses of patients with liver metastases, who historically have poorer prognosis among patients with NSCLC.Patients and methods: Patients were randomized 1 : 1 to nivolumab (3 mg/kg every 2 weeks) or docetaxel (75 mg/m2 every 3 weeks) until progression or discontinuation. The primary end point of each study was OS. Patients with baseline liver metastases were pooled across studies by treatment for subgroup analyses.Results: After 40.3 months' minimum follow-up in CheckMate 017 and 057, nivolumab continued to show an OS benefit versus docetaxel: estimated 3-year OS rates were 17{\%} [95{\%} confidence interval (CI), 14{\%} to 21{\%}] versus 8{\%} (95{\%} CI, 6{\%} to 11{\%}) in the pooled population with squamous or nonsquamous NSCLC. Nivolumab was generally well tolerated, with no new safety concerns identified. Of 854 randomized patients across both studies, 193 had baseline liver metastases. Nivolumab resulted in improved OS compared with docetaxel in patients with liver metastases (hazard ratio, 0.68; 95{\%} CI, 0.50-0.91), consistent with findings from the overall pooled study population (hazard ratio, 0.70; 95{\%} CI, 0.61-0.81). Rates of treatment-related hepatic adverse events (primarily grade 1-2 liver enzyme elevations) were slightly higher in nivolumab-treated patients with liver metastases (10{\%}) than in the overall pooled population (6{\%}).Conclusions: After 3 years' minimum follow-up, nivolumab continued to demonstrate an OS benefit versus docetaxel in patients with advanced NSCLC. Similarly, nivolumab demonstrated an OS benefit versus docetaxel in patients with liver metastases, and remained well tolerated.Clinical trial registration: CheckMate 017: NCT01642004; CheckMate 057: NCT01673867.",
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TY - JOUR

T1 - Nivolumab versus docetaxel in previously treated advanced non-small-cell lung cancer (CheckMate 017 and CheckMate 057)

T2 - 3-year update and outcomes in patients with liver metastases

AU - Vokes, E E

AU - Ready, N

AU - Felip, E

AU - Horn, L

AU - Burgio, M A

AU - Antonia, S J

AU - Arén Frontera, O

AU - Gettinger, S

AU - Holgado, E

AU - Spigel, D

AU - Waterhouse, D

AU - Domine, M

AU - Garassino, M

AU - Chow, L Q M

AU - Blumenschein, G

AU - Barlesi, F

AU - Coudert, B

AU - Gainor, J

AU - Arrieta, O

AU - Brahmer, J

AU - Butts, C

AU - Steins, M

AU - Geese, W J

AU - Li, A

AU - Healey, D

AU - Crinò, L

PY - 2018/4/1

Y1 - 2018/4/1

N2 - Background: Long-term data with immune checkpoint inhibitors in non-small-cell lung cancer (NSCLC) are limited. Two phase III trials demonstrated improved overall survival (OS) and a favorable safety profile with the anti-programmed death-1 antibody nivolumab versus docetaxel in patients with previously treated advanced squamous (CheckMate 017) and nonsquamous (CheckMate 057) NSCLC. We report results from ≥3 years' follow-up, including subgroup analyses of patients with liver metastases, who historically have poorer prognosis among patients with NSCLC.Patients and methods: Patients were randomized 1 : 1 to nivolumab (3 mg/kg every 2 weeks) or docetaxel (75 mg/m2 every 3 weeks) until progression or discontinuation. The primary end point of each study was OS. Patients with baseline liver metastases were pooled across studies by treatment for subgroup analyses.Results: After 40.3 months' minimum follow-up in CheckMate 017 and 057, nivolumab continued to show an OS benefit versus docetaxel: estimated 3-year OS rates were 17% [95% confidence interval (CI), 14% to 21%] versus 8% (95% CI, 6% to 11%) in the pooled population with squamous or nonsquamous NSCLC. Nivolumab was generally well tolerated, with no new safety concerns identified. Of 854 randomized patients across both studies, 193 had baseline liver metastases. Nivolumab resulted in improved OS compared with docetaxel in patients with liver metastases (hazard ratio, 0.68; 95% CI, 0.50-0.91), consistent with findings from the overall pooled study population (hazard ratio, 0.70; 95% CI, 0.61-0.81). Rates of treatment-related hepatic adverse events (primarily grade 1-2 liver enzyme elevations) were slightly higher in nivolumab-treated patients with liver metastases (10%) than in the overall pooled population (6%).Conclusions: After 3 years' minimum follow-up, nivolumab continued to demonstrate an OS benefit versus docetaxel in patients with advanced NSCLC. Similarly, nivolumab demonstrated an OS benefit versus docetaxel in patients with liver metastases, and remained well tolerated.Clinical trial registration: CheckMate 017: NCT01642004; CheckMate 057: NCT01673867.

AB - Background: Long-term data with immune checkpoint inhibitors in non-small-cell lung cancer (NSCLC) are limited. Two phase III trials demonstrated improved overall survival (OS) and a favorable safety profile with the anti-programmed death-1 antibody nivolumab versus docetaxel in patients with previously treated advanced squamous (CheckMate 017) and nonsquamous (CheckMate 057) NSCLC. We report results from ≥3 years' follow-up, including subgroup analyses of patients with liver metastases, who historically have poorer prognosis among patients with NSCLC.Patients and methods: Patients were randomized 1 : 1 to nivolumab (3 mg/kg every 2 weeks) or docetaxel (75 mg/m2 every 3 weeks) until progression or discontinuation. The primary end point of each study was OS. Patients with baseline liver metastases were pooled across studies by treatment for subgroup analyses.Results: After 40.3 months' minimum follow-up in CheckMate 017 and 057, nivolumab continued to show an OS benefit versus docetaxel: estimated 3-year OS rates were 17% [95% confidence interval (CI), 14% to 21%] versus 8% (95% CI, 6% to 11%) in the pooled population with squamous or nonsquamous NSCLC. Nivolumab was generally well tolerated, with no new safety concerns identified. Of 854 randomized patients across both studies, 193 had baseline liver metastases. Nivolumab resulted in improved OS compared with docetaxel in patients with liver metastases (hazard ratio, 0.68; 95% CI, 0.50-0.91), consistent with findings from the overall pooled study population (hazard ratio, 0.70; 95% CI, 0.61-0.81). Rates of treatment-related hepatic adverse events (primarily grade 1-2 liver enzyme elevations) were slightly higher in nivolumab-treated patients with liver metastases (10%) than in the overall pooled population (6%).Conclusions: After 3 years' minimum follow-up, nivolumab continued to demonstrate an OS benefit versus docetaxel in patients with advanced NSCLC. Similarly, nivolumab demonstrated an OS benefit versus docetaxel in patients with liver metastases, and remained well tolerated.Clinical trial registration: CheckMate 017: NCT01642004; CheckMate 057: NCT01673867.

U2 - 10.1093/annonc/mdy041

DO - 10.1093/annonc/mdy041

M3 - Article

C2 - 29408986

VL - 29

SP - 959

EP - 965

JO - Annals of Oncology

JF - Annals of Oncology

SN - 0923-7534

IS - 4

ER -