Carboplatin and pemetrexed with or without pembrolizumab for advanced, non-squamous non-small-cell lung cancer: a randomised, phase 2 cohort of the open-label KEYNOTE-021 study

The Lancet Oncology

Volumn 17, Issue 11, 2016, Pages 1497-1508

  Langer, Corey J ^a   Gadgeel, Shirish M ^b   Borghaei, Hossein ^c   Papadimitrakopoulou, Vassiliki A ^d   Patnaik, Amita ^e   Powell, Steven F ^f   Gentzler, Ryan D ^g   Martins, Renato G ^h   Stevenson, James P ⁱ   Jalal, Shadia I ^j   Panwalkar, Amit ^k   Yang, James Chih Hsin ^l   Gubens, Matthew ^m   Sequist, Lecia V ⁿ   Awad, Mark M ^o   Fiore, Joseph ^q   Ge, Yang ^q   Raftopoulos, Harry ^q   Gandhi, Leena ^o,p  

^a UNIVERSITY OF PENNSYLVANIA   (United States)

^b KARMANOS CANCER INSTITUTE   (United States)

^c FOX CHASE CANCER CENTER   (United States)

^d UNIVERSITY OF TEXAS MD ANDERSON CANCER CENTER   (United States)

^e South Texas Accelerated Research Therapeutics   (United States)

^f Sanford Medical Center   (United States)

^g UNIVERSITY OF VIRGINIA   (United States)

^h SEATTLE CANCER CARE ALLIANCE   (United States)

ⁱ LERNER RESEARCH INSTITUTE   (United States)

^j INDIANA UNIVERSITY SCHOOL OF MEDICINE   (United States)

^k MeritCare Roger Maris Cancer Center   (United States)

^l NATIONAL TAIWAN UNIVERSITY HOSPITAL   (Taiwan)

^m UNIVERSITY OF CALIFORNIA   (United States)

ⁿ MASSACHUSETTS GENERAL HOSPITAL CANCER CENTER   (United States)

^o DANA FARBER CANCER INSTITUTE   (United States)

^p NEW YORK UNIVERSITY MEDICAL CENTER   (United States)

^q MERCK RESEARCH LABORATORIES   (United States)

more..

Author keywords

[No Author keywords available]

Indexed keywords

CARBOPLATIN; EPIDERMAL GROWTH FACTOR RECEPTOR; PEMBROLIZUMAB; PEMETREXED; PROGRAMMED DEATH 1 LIGAND 1; ANTINEOPLASTIC AGENT; MONOCLONAL ANTIBODY;

ACUTE KIDNEY FAILURE; ADULT; ADVANCED CANCER; AGED; ALK GENE; ANEMIA; AREA UNDER THE CURVE; ARTICLE; CANCER CHEMOTHERAPY; CANCER STAGING; COHORT ANALYSIS; CONTROLLED STUDY; DRUG EFFICACY; DRUG FATALITY; DRUG SAFETY; DRUG TOLERABILITY; EGFR GENE; FATIGUE; FEMALE; FOLLOW UP; GENE; GENETIC VARIABILITY; HUMAN; INCIDENCE; INTENTION TO TREAT ANALYSIS; LYMPHOCYTE COUNT; MAINTENANCE THERAPY; MAJOR CLINICAL STUDY; MALE; MIDDLE AGED; MULTIPLE CYCLE TREATMENT; NEUTROPENIA; NEUTROPHIL COUNT; NON SMALL CELL LUNG CANCER; OPEN STUDY; OUTCOME ASSESSMENT; PANCYTOPENIA; PHASE 2 CLINICAL TRIAL; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; RESPONSE EVALUATION CRITERIA IN SOLID TUMORS; SEPSIS; TAIWAN; THROMBOCYTOPENIA; TREATMENT DURATION; TREATMENT RESPONSE; UNITED STATES; CARCINOMA, NON-SMALL-CELL LUNG; CLINICAL TRIAL; LUNG NEOPLASMS; MULTICENTER STUDY;

AGED; ANTIBODIES, MONOCLONAL, HUMANIZED; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; CARBOPLATIN; CARCINOMA, NON-SMALL-CELL LUNG; FEMALE; HUMANS; LUNG NEOPLASMS; MALE; MIDDLE AGED; PEMETREXED;

EID: 84994430500     PISSN: 14702045     EISSN: 14745488     Source Type: Journal    
DOI: 10.1016/S1470-2045(16)30498-3     Document Type: Article

References (29)

1. 1 Sandler, A, Gray, R, Perry, MC, et al. Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med 355 (2006), 2542–2550.
2. 2 Reck, M, von Pawel, J, Zatloukal, P, et al. Overall survival with cisplatin-gemcitabine and bevacizumab or placebo as first-line therapy for nonsquamous non-small-cell lung cancer: results from a randomised phase III trial (AVAiL). Ann Oncol 21 (2010), 1804–1809.
3. 3 Garon, EB, Rizvi, NA, Hui, R, et al. Pembrolizumab for the treatment of non-small-cell lung cancer. N Engl J Med 372 (2015), 2018–2028.
4. 4 Chatterjee, M, Turner, DC, Felip, E, et al. Systematic evaluation of pembrolizumab dosing in patients with advanced non-small-cell lung cancer. Ann Oncol 27 (2016), 1921–1928.
5. 5 Herbst, RS, Baas, P, Kim, DW, et al. Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial. Lancet 387 (2016), 1540–1550.
6. 6 Gettinger, S, Rizvi, NA, Chow, LQ, et al. Nivolumab monotherapy for first-line treatment of advanced non-small-cell lung cancer. J Clin Oncol 34 (2016), 2980–2987.
7. 7 Gettinger, SN, Horn, L, Gandhi, L, et al. 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 Clin Oncol 33 (2015), 2004–2012.
8. 8 Borghaei, H, Paz-Ares, L, Horn, L, et al. Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer. N Engl J Med 373 (2015), 1627–1639.
9. 9 Brahmer, J, Reckamp, KL, Baas, P, et al. Nivolumab versus docetaxel in advanced squamous-cell non-small-cell lung cancer. N Engl J Med 373 (2015), 123–135.
10. 10 Fehrenbacher, L, Spira, A, Ballinger, M, et al. Atezolizumab versus docetaxel for patients with previously treated non-small-cell lung cancer (POPLAR): a multicentre, open-label, phase 2 randomised controlled trial. Lancet 387 (2016), 1837–1846.
11. 11 Zitvogel, L, Galluzzi, L, Smyth, MJ, Kroemer, G, Mechanism of action of conventional and targeted anticancer therapies: reinstating immunosurveillance. Immunity 39 (2013), 74–88.
12. 12 Galluzzi, L, Buque, A, Kepp, O, Zitvogel, L, Kroemer, G, Immunological effects of conventional chemotherapy and targeted anticancer agents. Cancer Cell 28 (2015), 690–714.
13. 13 Apetoh, L, Ladoire, S, Coukos, G, Ghiringhelli, F, Combining immunotherapy and anticancer agents: the right path to achieve cancer cure?. Ann Oncol 26 (2015), 1813–1823.
14. 14 Peng, J, Hamanishi, J, Matsumura, N, et al. Chemotherapy induces programmed cell death-ligand 1 overexpression via the nuclear factor-kappaB to foster an immunosuppressive tumor microenvironment in ovarian cancer. Cancer Res 75 (2015), 5034–5045.
15. 15 Grabosch, S, Zeng, F, Zhang, L, et al. PD-L1 biology in response to chemotherapy in vitro and in vivo in ovarian cancer. J Immunother Cancer, 3, 2015, P302.
16. 16 Zhang, P, Ma, Y, Lv, C, et al. The up-regulation of PD-L1 promotes the resistant response in non-small cell lung cancer patients with neo-adjuvant chemotherapy. Cancer Sci, 2016, 10.1111/cas.13072 published online Sept 1.
17. 17 Rizvi, NA, Hellmann, MD, Brahmer, JR, et al. Nivolumab in combination with platinum-based doublet chemotherapy for first-line treatment of advanced non-small-cell lung cancer. J Clin Oncol 34 (2016), 2969–2979.
18. 18 Gadgeel, SM, Stevenson, J, Langer, CJ, et al. Pembrolizumab (pembro) plus chemotherpay as front-line therapy for advanced NSCLC: KEYNOTE-021 cohorts A-C. Proc Am Soc Clin Oncol, 34, 2016 Abstr 9016.
19. 19 Camidge, DR, Liu, SV, Powderly, JD, et al. Atezolizumab (MPDL3280A) combined with platinum-based chemotherapy in non-small cell lung cancer (NSCLC): a phase 1b study. J Thorac Oncol, 10, 2015 Abstr 02.7.
20. 20 Eisenhauer, EA, Therasse, P, Bogaerts, J, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 45 (2009), 228–247.
21. 21 Dako. PD-L1 IHC 22C3 pharmDx [product information], 2015, Dako North America Inc, Carpinteria, CA.
22. 22 Roach, C, Zhang, N, Corigliano, E, et al. Development of a companion diagnostic PD-L1 immunohistochemistry assay for pembrolizumab therapy in non-small-cell lung cancer. Appl Immunohistochem Mol Morphol 24 (2016), 392–397.
23. 23 Farrington, CP, Manning, G, Test statistics and sample size formulae for comparative binomial trials with null hypothesis of non-zero risk difference or non-unity relative risk. Stat Med 9 (1990), 1447–1454.
24. 24 Marcus, R, Peritz, E, Gabriel, KR, On closed testing procedures with special reference to ordered analysis of variance. Biometrika 63 (1976), 655–660.
25. 25 Schuette, WH, Groschel, A, Sebastian, M, et al. A randomized phase II study of pemetrexed in combination with cisplatin or carboplatin as first-line therapy for patients with locally advanced or metastatic non-small-cell lung cancer. Clin Lung Cancer 14 (2013), 215–223.
26. 26 Zinner, RG, Obasaju, CK, Spigel, DR, et al. PRONOUNCE: randomized, open-label, phase III study of first-line pemetrexed + carboplatin followed by maintenance pemetrexed versus paclitaxel + carboplatin + bevacizumab followed by maintenance bevacizumab in patients ith advanced nonsquamous non-small-cell lung cancer. J Thorac Oncol 10 (2015), 134–142.
27. 27 Wheatley-Price, P, Blackhall, F, Lee, SM, et al. The influence of sex and histology on outcomes in non-small-cell lung cancer: a pooled analysis of five randomized trials. Ann Oncol 21 (2010), 2023–2028.
28. 28 Wakelee, HA, Dahlberg, SE, Brahmer, JR, et al. Differential effect of age on survival in advanced NSCLC in women versus men: analysis of recent Eastern Cooperative Oncology Group (ECOG) studies, with and without bevacizumab. Lung Cancer 76 (2012), 410–415.
29. 29 Paz-Ares, L, de Marinis, F, Dediu, M, et al. Maintenance therapy with pemetrexed plus best supportive care versus placebo plus best supportive care after induction therapy with pemetrexed plus cisplatin for advanced non-squamous non-small-cell lung cancer (PARAMOUNT): a double-blind, phase 3, randomised controlled trial. Lancet Oncol 13 (2012), 247–255.