Adjuvant pembrolizumab versus placebo in resected stage III melanoma

New England Journal of Medicine

Volumn 378, Issue 19, 2018, Pages 1789-1801

  Eggermont, Alexander M M ^a   Blank, Christian U ^d   Mandala, Mario ^g   Long, Georgina V ⁱ   Atkinson, Victoria ^j   Dalle, Stéphane ^b   Haydon, Andrew ^a   Lichinitser, Mikhail ^o   Khattak, Adnan ^k,m   Carlino, Matteo S ^j   Sandhu, Shahneen ^l   Larkin, James ^n,p   Puig, Susana ^a   Ascierto, Paolo A ^h   Rutkowski, Piotr ^r   Schadendorf, Dirk ^s   Koornstra, Rutger ^f   Hernandez Aya, Leonel ^t   Maio, Michele ^l   Van Den Eertwegh, Alfonsus J M ^e   Grob, Jean Jacques ^c   Gutzmer, Ralf ^a   Jamal, Rahima ^u,v   Lorigan, Paul ^w   Ibrahim, Nageatte ^x   Marreaud, Sandrine ^y   Van Akkooi, Alexander C J ^d   Suciu, Stefan ^b,q,y   Robert, Caroline ^a   more..

^a INSTITUT GUSTAVE ROUSSY   (France)

^b CENTRE DE RECHERCHE EN CANCÉROLOGIE DE LYON   (France)

^c AIX MARSEILLE UNIVERSITY   (France)

^d NETHERLANDS CANCER INSTITUTE   (Netherlands)

^e VU UNIVERSITY MEDICAL CENTER   (Netherlands)

^f RADBOUD UNIVERSITY MEDICAL CENTER   (Netherlands)

^g Unit of Nephrology and Dialysis   (Italy)

^h NATIONAL CANCER INSTITUTE   (Italy)

ⁱ UNIVERSITY HOSPITAL OF SIENA   (Italy)

^j UNIVERSITY OF SYDNEY   (Australia)

^k UNIVERSITY OF QUEENSLAND   (Australia)

^l ALFRED HOSPITAL   (Australia)

^m PETER MACCALLUM CANCER CENTRE   (Australia)

ⁿ UNIVERSITY OF WESTERN AUSTRALIA   (Australia)

^o Chemotherapy Department   (Russian Federation)

^p ROYAL MARSDEN HOSPITAL   (United Kingdom)

^q HOSPITAL CLÍNIC   (Spain)

^r INSTITUTE OF ONCOLOGY   (Poland)

^s UNIVERSITY HOSPITAL ESSEN   (Germany)

^t HANNOVER MEDICAL SCHOOL   (Germany)

^u WASHINGTON UNIVERSITY SCHOOL OF MEDICINE   (United States)

^v CENTRE HOSPITALIER DE L UNIVERSITÉ DE MONTRÉAL   (Canada)

^w CHRISTIE HOSPITAL   (United Kingdom)

^x MERCK RESEARCH LABORATORIES   (United States)

^y European Organisation of Research and Treatment of Cancer   (Belgium)

more..

Author keywords

[No Author keywords available]

Indexed keywords

PEMBROLIZUMAB; PLACEBO; PROGRAMMED DEATH 1 LIGAND 1; CD274 PROTEIN, HUMAN; IMMUNOLOGICAL ADJUVANT; MONOCLONAL ANTIBODY;

ADULT; AGED; ARTHRALGIA; ARTICLE; ASTHENIA; CANCER ADJUVANT THERAPY; CANCER STAGING; COLITIS; CONTROLLED STUDY; CUTANEOUS MELANOMA; DIARRHEA; DISTANT METASTASIS; DOUBLE BLIND PROCEDURE; DRUG EFFICACY; DRUG SAFETY; DYSPNEA; ENDOCRINE DISEASE; FATIGUE; FEMALE; FOLLOW UP; HEPATITIS; HIGH RISK PATIENT; HUMAN; INTENTION TO TREAT ANALYSIS; INTERSTITIAL LUNG DISEASE; MAJOR CLINICAL STUDY; MALE; MYOCARDITIS; MYOSITIS; NAUSEA; NEPHRITIS; PANCREATITIS; PHASE 3 CLINICAL TRIAL; PNEUMONIA; PRIORITY JOURNAL; PRURITUS; RANDOMIZED CONTROLLED TRIAL; RASH; RECURRENCE FREE SURVIVAL; SARCOIDOSIS; SKIN MANIFESTATION; UVEITIS; ANTAGONISTS AND INHIBITORS; CLINICAL TRIAL; COMPARATIVE STUDY; DISEASE FREE SURVIVAL; INTRAVENOUS DRUG ADMINISTRATION; KAPLAN MEIER METHOD; MELANOMA; MIDDLE AGED; MORTALITY; MULTICENTER STUDY; QUALITY OF LIFE; SKIN TUMOR; SURVIVAL RATE; TUMOR RECURRENCE; VERY ELDERLY;

ADJUVANTS, IMMUNOLOGIC; ADULT; AGED; AGED, 80 AND OVER; ANTIBODIES, MONOCLONAL, HUMANIZED; B7-H1 ANTIGEN; DISEASE-FREE SURVIVAL; DOUBLE-BLIND METHOD; FEMALE; HUMANS; INFUSIONS, INTRAVENOUS; INTENTION TO TREAT ANALYSIS; KAPLAN-MEIER ESTIMATE; MALE; MELANOMA; MIDDLE AGED; NEOPLASM RECURRENCE, LOCAL; NEOPLASM STAGING; QUALITY OF LIFE; SKIN NEOPLASMS; SURVIVAL RATE;

EID: 85046890226     PISSN: 00284793     EISSN: 15334406     Source Type: Journal    
DOI: 10.1056/NEJMoa1802357     Document Type: Article

References (30)

1. Eggermont AMM, Spatz A, Robert C. Cutaneous melanoma. Lancet 2014; 383: 816-27.
2. Robert C, Karaszewska B, Schachter J, et al. Improved overall survival in melanoma with combined dabrafenib and trametinib. N Engl J Med 2015; 372: 30-9.
3. Hodi FS, O'Day SJ, McDermott DF, et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med 2010; 363: 711-23.
4. Robert C, Long GV, Brady B, et al. Nivolumab in previously untreated melanoma without BRAF mutation. N Engl J Med 2015; 372: 320-30.
5. Robert C, Schachter J, Long GV, et al. Pembrolizumab versus ipilimumab in advanced melanoma. N Engl J Med 2015; 372:2521-32.
6. Ugurel S, Röhmel J, Ascierto PA, et al. Survival of patients with advanced meta-static melanoma: the impact of novel therapies - update 2017. Eur J Cancer 2017; 83:247-57.
7. Eggermont AM, Chiarion-Sileni V, Grob JJ, et al. Adjuvant ipilimumab versus placebo after complete resection of high-risk stage III melanoma (EORTC 18071): a randomised, double-blind, phase 3 trial. Lancet Oncol 2015; 16:522-30.
8. Eggermont AMM, Chiarion-Sileni V, Grob J-J, et al. Prolonged survival in stage III melanoma with ipilimumab adjuvant therapy. N Engl J Med 2016; 375: 1845-55.
9. Long GV, Hauschild A, Santinami M, et al. Adjuvant dabrafenib plus trametinib in stage III BRAF-mutated melanoma. N Engl J Med 2017; 377: 1813-23.
10. Weber J, Mandala M, Del Vecchio M, et al. Adjuvant nivolumab versus ipilimumab in resected stage III or IV melanoma. N Engl J Med 2017; 377: 1824-35.
11. van Akkooi ACJ, Nowecki ZI, Voit C, et al. Sentinel node tumor burden according to the Rotterdam criteria is the most important prognostic factor for survival in melanoma patients: a multicenter study in 388 patients with positive sentinel nodes. Ann Surg 2008; 248: 949-55.
12. van der Ploeg APT, van Akkooi ACJ, Rutkowski P, et al. Prognosis in patients with sentinel node-positive melanoma is accurately defined by the combined Rotterdam tumor load and Dewar topography criteria. J Clin Oncol 2011; 29: 2206-14.
13. van der Ploeg APT, van Akkooi AC, Haydu LE, et al. The prognostic significance of sentinel node tumour burden in melanoma patients: an international, multicenter study of 1539 sentinel node-positive melanoma patients. Eur J Cancer 2014; 50:111-20.
14. Balch CM, Gershenwald JE, Soong S-J, et al. Final version of 2009 AJCC melanoma staging and classification. J Clin Oncol 2009; 27:6199-206.
15. Daud AI, Wolchok JD, Robert C, et al. Programmed death-ligand 1 expression and response to the anti-programmed death 1 antibody pembrolizumab in melanoma. J Clin Oncol 2016; 34: 4102-9.
16. Spiessens B, Debois M. Adjusted significance levels for subgroup analyses in clinical trials. Contemp Clin Trials 2010; 31: 647-56.
17. O'Brien PC, Fleming TR. A multiple testing procedure for clinical trials. Biomet rics 1979; 35:549-56.
18. Eggermont AMM, Dummer R. The 2017 complete overhaul of adjuvant therapies for high-risk melanoma and its consequences for staging and management of melanoma patients. Eur J Cancer 2017; 86:101-5.
19. Suciu S, Eggermont AMM, Lorigan P, et al. Relapse-free survival as a surrogate for overall survival in the evaluation of stage II-III melanoma adjuvant therapy. J Natl Cancer Inst 2018; 110: 87-96.
20. Hofmann L, Forschner A, Loquai C, et al. Cutaneous, gastrointestinal, hepatic, endocrine, and renal side-effects of anti-PD-1 therapy. Eur J Cancer 2016; 60: 190-209.
21. Zimmer L, Goldinger SM, Hofmann L, et al. Neurological, respiratory, musculo-skeletal, cardiac and ocular side-effects of anti-PD-1 therapy. Eur J Cancer 2016; 60: 210-25.
22. Eggermont AMM, Suciu S, Santinami M, et al. Adjuvant therapy with pegylated interferon alfa-2b versus observation alone in resected stage III melanoma: final results of EORTC 18991, a randomised phase III trial. Lancet 2008; 372: 117-26.
23. Eggermont AM, Suciu S, Testori A, et al. Long-term results of the randomized phase III trial EORTC 18991 of adjuvant therapy with pegylated interferon alfa-2b versus observation in resected stage III melanoma. J Clin Oncol 2012; 30:3810-8.
24. Eggermont AMM, Suciu S, MacKie R, et al. Post-surgery adjuvant therapy with intermediate doses of interferon alfa 2b versus observation in patients with stage IIb/III melanoma (EORTC 18952): randomised controlled trial. Lancet 2005; 366: 1189-96.
25. Eggermont AMM, Suciu S, Testori A, et al. Ulceration and stage are predictive of interferon efficacy in melanoma: results of the phase III adjuvant trials EORTC 18952 and EORTC 18991. Eur J Cancer 2012; 48:218-25.
26. Eggermont AM, Suciu S, Rutkowski P, et al. Long term follow up of the EORTC 18952 trial of adjuvant therapy in resected stage IIB-III cutaneous melanoma patients comparing intermediate doses of interfer-on-alpha-2b (IFN) with observation: ulceration of primary is key determinant for IFN-sensitivity. Eur J Cancer 2016; 55: 111-21.
27. Ives NJ, Suciu S, Eggermont AMM, et al. Adjuvant interferon-α for the treatment of high-risk melanoma: an individual patient data meta-analysis. Eur J Cancer 2017; 82:171-83.
28. Garbe C, Peris K, Hauschild A, et al. Diagnosis and treatment of melanoma: European consensus-based interdisciplinary guideline - update 2016. Eur J Cancer 2016; 63:201-17.
29. Leiter U, Stadler R, Mauch C, et al. Complete lymph node dissection versus no dissection in patients with sentinel lymph node biopsy positive melanoma (DeCOG-SLT): a multicentre, randomised, phase 3 trial. Lancet Oncol 2016; 17: 757-67.
30. Faries MB, Thompson JF, Cochran AJ, et al. Completion dissection or observation for sentinel-node metastasis in melanoma. N Engl J Med 2017; 376: 2211-22.