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

. 2015 Jul 09 ; 373 (2) : 123-35. [epub] 20150531

Jazyk angličtina Země Spojené státy americké Médium print-electronic

Typ dokumentu klinické zkoušky, fáze III, srovnávací studie, časopisecké články, multicentrická studie, randomizované kontrolované studie, práce podpořená grantem

Perzistentní odkaz   https://www.medvik.cz/link/pmid26028407

Grantová podpora
P30 CA076292 NCI NIH HHS - United States

BACKGROUND: Patients with advanced squamous-cell non-small-cell lung cancer (NSCLC) who have disease progression during or after first-line chemotherapy have limited treatment options. This randomized, open-label, international, phase 3 study evaluated the efficacy and safety of nivolumab, a fully human IgG4 programmed death 1 (PD-1) immune-checkpoint-inhibitor antibody, as compared with docetaxel in this patient population. METHODS: We randomly assigned 272 patients 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: The median overall survival was 9.2 months (95% confidence interval [CI], 7.3 to 13.3) with nivolumab versus 6.0 months (95% CI, 5.1 to 7.3) with docetaxel. The risk of death was 41% lower with nivolumab than with docetaxel (hazard ratio, 0.59; 95% CI, 0.44 to 0.79; P<0.001). At 1 year, the overall survival rate was 42% (95% CI, 34 to 50) with nivolumab versus 24% (95% CI, 17 to 31) with docetaxel. The response rate was 20% with nivolumab versus 9% with docetaxel (P=0.008). The median progression-free survival was 3.5 months with nivolumab versus 2.8 months with docetaxel (hazard ratio for death or disease progression, 0.62; 95% CI, 0.47 to 0.81; P<0.001). The expression of the PD-1 ligand (PD-L1) was neither prognostic nor predictive of benefit. Treatment-related adverse events of grade 3 or 4 were reported in 7% of the patients in the nivolumab group as compared with 55% of those in the docetaxel group. CONCLUSIONS: Among patients with advanced, previously treated squamous-cell NSCLC, overall survival, response rate, and progression-free survival were significantly better with nivolumab than with docetaxel, regardless of PD-L1 expression level. (Funded by Bristol-Myers Squibb; CheckMate 017 ClinicalTrials.gov number, NCT01642004.).

Komentář v

PubMed

Zobrazit více v PubMed

Travis WD. Pathology of lung cancer. Clin Chest Med. 2011;32:669–92. PubMed

Fossella FV, DeVore R, Kerr RN, et al. 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: the TAX 320 Non-Small Cell Lung Cancer Study Group. J Clin Oncol. 2000;18:2354–62. PubMed

Shepherd FA, Dancey J, Ramlau R, et al. Prospective randomized trial of docetaxel versus best supportive care in patients with non-small-cell lung cancer previously treated with platinum-based chemotherapy. J Clin Oncol. 2000;18:2095–103. PubMed

Taxotere (docetaxel) U S prescribing information. Bridgewater, NJ: Sanofi-Aventis; May 2010, http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/020449s059lbl.pdf.

National Comprehensive Cancer Network (NCCN) Non-small cell lung cancer guidelines, v4. 2015 http://www.nccn.org/professionals/physician_gls/f_guidelines.asp#nscl.

Kim ES, Hirsh V, Mok T, et al. Gefitinib versus docetaxel in previously treated non-small-cell lung cancer (INTEREST): a randomised phase III trial. Lancet. 2008;372:1809–18. PubMed

Hanna N, Shepherd FA, Fossella FV, et al. Randomized phase III trial of pemetrexed versus docetaxel in patients with non-small-cell lung cancer previously treated with chemotherapy. J Clin Oncol. 2004;22:1589–97. PubMed

Pardoll DM. The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer. 2012;12:252–64. PubMed PMC

Chen YB, Mu CY, Huang JA. Clinical significance of programmed death-1 ligand-1 expression in patients with non-small cell lung cancer: a 5-year-follow-up study. Tumori. 2012;98:751–5. PubMed

Velcheti V, Schalper KA, Carvajal DE, et al. Programmed death ligand-1 expression in non-small cell lung cancer. Lab Invest. 2014;94:107–16. PubMed PMC

Brahmer JR, Drake CG, Wollner I, et al. Phase I study of single-agent anti-programmed death-1 (MDX-1106) in refractory solid tumors: safety, clinical activity, pharmacodynamics, and immunologic correlates. J Clin Oncol. 2010;28:3167–75. PubMed PMC

Wang C, Thudium KB, Han M, et al. In vitro characterization of the anti-PD-1 antibody nivolumab, BMS-936558, and in vivo toxicology in non-human primates. Cancer Immunol Res. 2014;2:846–56. PubMed

Topalian SL, Hodi FS, Brahmer JR, et al. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med. 2012;366:2443–54. PubMed PMC

Gettinger SN, Horn L, Gandhi L, et al. Overall survival and long-term safety of nivolumab (anti-PD-1 antibody, BMS-936558, ONO-4538) in patients with previously treated advanced non-small-cell lung cancer. J Clin Oncol. 2015 Apr 20; Epub ahead of print. PubMed PMC

Rizvi NA, Mazières J, Planchard D, et al. Activity and safety of nivolumab, an anti-PD-1 immune checkpoint inhibitor, for patients with advanced, refractory squamous non-small-cell lung cancer (CheckMate 063): a phase 2, single-arm trial. Lancet Oncol. 2015;16:257–65. PubMed PMC

Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1) Eur J Cancer. 2009;45:228–47. PubMed

Penrod JR, Korytowsky B, Petrilla A, et al. Survival of U.S. Medicare patients with advanced non small cell lung cancer by line of therapy. J Clin Oncol. 2014;32:15. Suppl. abstract.

Garon EB, Ciuleanu TE, Arrieta O, et al. 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. Lancet. 2014;384:665–73. PubMed

Cyramza (ramucirumab) U S prescribing information. Indianapolis: Eli Lilly; Dec 2014, http://pi.lilly.com/us/cyramza-pi.pdf.

FDA expands approved use of Opdivo to treat lung cancer. Press release of the Food and Drug Administration; Bethesda, MD: Mar 4, 2015. http://www.fda.gov/newsevents/newsroom/pressannouncements/ucm436534.htm.

Garon EB, Gandhi L, Rizvi N, et al. Antitumor activity of pembrolizumab (Pembro; MK-3475) and correlation with programmed death ligand 1 (PD-L1) expression in a pooled analysis of patients (pts) with advanced non-small cell lung carcinoma (NSCLC) Ann Oncol. 2014;25 Suppl 5. abstract.

Herbst RS, Soria JC, Kowanetz M, et al. Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients. Nature. 2014;515:563–7. PubMed PMC

Soria JC, Cruz C, Bahleda R, et al. Clinical activity, safety and biomarkers of PD-L1 blockade in non-small cell lung cancer (NSCLC): additional analyses from a clinical study of the engineered antibody MPDL3280A (anti-PDL1) Eur J Cancer. 2013;49 Suppl 2. abstract.

Rizvi NA, Hellmann MD, Snyder A, et al. Cancer immunology: mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer. Science. 2015;348:124–8. PubMed PMC

Nejnovějších 20 citací...

Zobrazit více v
Medvik | PubMed

Pembrolizumab in Patients with Advanced Urothelial Carcinoma with ECOG Performance Status 2: A Real-World Study from the ARON-2 Project

. 2024 Sep ; 19 (5) : 747-755. [epub] 20240806

Engineering PD-1-targeted small protein variants for in vitro diagnostics and in vivo PET imaging

. 2024 May 06 ; 22 (1) : 426. [epub] 20240506

Serious Immune-related Adverse Events Are Associated With Greater Efficacy of Nivolumab Therapy Against Non-small Cell Lung Cancer

. 2023 Sep-Oct ; 37 (5) : 2229-2236.

Insomnia in patients treated with checkpoint inhibitors for cancer: A meta-analysis

. 2022 ; 12 () : 946307. [epub] 20220802

Applications of Liquid Biopsies in Non-Small-Cell Lung Cancer

. 2022 Jul 25 ; 12 (8) : . [epub] 20220725

Incidence of fatigue associated with immune checkpoint inhibitors in patients with cancer: a meta-analysis

. 2022 Jun ; 7 (3) : 100474. [epub] 20220513

Update on PD-1/PD-L1 Inhibitors in Multiple Myeloma

. 2018 ; 9 () : 2431. [epub] 20181116

Nivolumab induced encephalopathy in a man with metastatic renal cell cancer: a case report

. 2018 Sep 15 ; 12 (1) : 262. [epub] 20180915

PD-1/PD-L1 inhibitors in haematological malignancies: update 2017

. 2017 Nov ; 152 (3) : 357-371. [epub] 20170804

Expression of Programmed Cell Death Protein 1 by Tumor-Infiltrating Lymphocytes and Tumor Cells is Associated with Advanced Tumor Stage in Patients with Esophageal Adenocarcinoma

. 2017 Sep ; 24 (9) : 2698-2706. [epub] 20170420

Trial watch: Immune checkpoint blockers for cancer therapy

. 2017 ; 6 (11) : e1373237. [epub] 20170831

Neopterin as a biomarker of immune response in cancer patients

. 2017 Jul ; 5 (13) : 280.

First-Line Nivolumab in Stage IV or Recurrent Non-Small-Cell Lung Cancer

. 2017 Jun 22 ; 376 (25) : 2415-2426.

PD-1/PD-L1 inhibitors in multiple myeloma: The present and the future

. 2016 ; 5 (12) : e1254856. [epub] 20161108

Zobrazit více v PubMed

ClinicalTrials.gov
NCT01642004

Najít záznam

Citační ukazatele

Nahrávání dat ...

Možnosti archivace

Nahrávání dat ...