Pembrolizumab versus ipilimumab for advanced melanoma: final overall survival results of a multicentre, randomised, open-label phase 3 study (KEYNOTE-006)

The Lancet

Volumn 390, Issue 10105, 2017, Pages 1853-1862

  Schachter, Jacob ^a   Ribas, Antoni ^b   Long, Georgina V ^c   Arance, Ana ^d   Grob, Jean Jacques ^e   Mortier, Laurent ^f   Daud, Adil ^g   Carlino, Matteo S ^c   McNeil, Catriona ^h   Lotem, Michal ⁱ   Larkin, James ^j   Lorigan, Paul ^k   Neyns, Bart ^l   Blank, Christian ^m   Petrella, Teresa M ⁿ   Hamid, Omid ^o   Zhou, Honghong ^p   Ebbinghaus, Scot ^p   Ibrahim, Nageatte ^p   Robert, Caroline ^q  

^a SHEBA MEDICAL CENTER   (Israel)

^b UNIVERSITY OF CALIFORNIA   (United States)

^c UNIVERSITY OF SYDNEY   (Australia)

^d HOSPITAL CLÍNIC   (Spain)

^e AIX MARSEILLE UNIVERSITY   (France)

^f UNIV LILLE   (France)

^g UNIVERSITY OF CALIFORNIA   (United States)

^h ROYAL PRINCE ALFRED HOSPITAL   (Australia)

ⁱ HADASSAH HEBREW UNIVERSITY MEDICAL CENTER   (Israel)

^j ROYAL MARSDEN HOSPITAL   (United Kingdom)

^k CHRISTIE HOSPITAL   (United Kingdom)

^l UNIVERSITY HOSPITAL BRUSSELS   (Belgium)

^m NETHERLANDS CANCER INSTITUTE   (Netherlands)

ⁿ SUNNYBROOK RESEARCH INSTITUTE   (Canada)

^o Angeles Clinic and Research Institute   (United States)

^p MERCK RESEARCH LABORATORIES   (United States)

^q UNIVERSITÉ PARIS SACLAY   (France)

more..

Author keywords

[No Author keywords available]

Indexed keywords

IPILIMUMAB; PEMBROLIZUMAB; IMMUNOLOGICAL ANTINEOPLASTIC AGENT; MONOCLONAL ANTIBODY;

ADULT; ADVANCED CANCER; AGED; ARTHRALGIA; ARTICLE; AUSTRALIA; AUSTRIA; BELGIUM; CANADA; CANCER CENTER; CANCER PATIENT; CANCER STAGING; CANCER SURVIVAL; CHILE; COLITIS; COLOMBIA; COMPARATIVE EFFECTIVENESS; COMPARATIVE STUDY; CONTROLLED STUDY; CORTICOSTEROID THERAPY; DIARRHEA; DRUG SAFETY; DRUG WITHDRAWAL; ENDOCRINE DISEASE; FATIGUE; FEMALE; FOLLOW UP; FRANCE; GERMANY; HEPATITIS; HUMAN; HYPERTHYROIDISM; HYPOTHYROIDISM; IMMUNOHISTOCHEMISTRY; INTENTION TO TREAT ANALYSIS; INTERSTITIAL NEPHRITIS; ISRAEL; MAJOR CLINICAL STUDY; MALE; MELANOMA; MIDDLE AGED; MULTICENTER STUDY; NAUSEA; NETHERLANDS; NEW ZEALAND; NORWAY; NUCLEAR MAGNETIC RESONANCE IMAGING; OPEN STUDY; OUTCOME ASSESSMENT; OVERALL SURVIVAL; PHASE 3 CLINICAL TRIAL; PNEUMONIA; PRIORITY JOURNAL; PROGRESSION FREE SURVIVAL; PRURITUS; RANDOMIZED CONTROLLED TRIAL; RASH; RESPONSE EVALUATION CRITERIA IN SOLID TUMORS; SPAIN; SURVIVAL ANALYSIS; SWEDEN; SYSTEMIC THERAPY; THYROIDITIS; TREATMENT DURATION; UNITED KINGDOM; UNITED STATES; ADOLESCENT; CHEMICALLY INDUCED; CLINICAL TRIAL; DRUG ADMINISTRATION; MORTALITY; PATHOLOGY; SKIN TUMOR; TOXIC HEPATITIS; VERY ELDERLY; YOUNG ADULT;

ADOLESCENT; ADULT; AGED; AGED, 80 AND OVER; ANTIBODIES, MONOCLONAL, HUMANIZED; ANTINEOPLASTIC AGENTS, IMMUNOLOGICAL; CHEMICAL AND DRUG INDUCED LIVER INJURY; COLITIS; DRUG ADMINISTRATION SCHEDULE; ENDOCRINE SYSTEM DISEASES; FEMALE; HUMANS; IPILIMUMAB; MALE; MELANOMA; MIDDLE AGED; SKIN NEOPLASMS; YOUNG ADULT;

EID: 85027501801     PISSN: 01406736     EISSN: 1474547X     Source Type: Journal    
DOI: 10.1016/S0140-6736(17)31601-X     Document Type: Article

References (34)

1. Pardoll, DM, The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer 12 (2012), 252–264.
2. Yervoy [package insert], 2015, Bristol-Myers Squibb, Princeton, NJ, USA.
3. Keytruda [package insert], 2016, Merck Sharp & Dohme Corp, Kenilworth, NJ, USA.
4. Opdivo [package insert], 2016, Bristol-Myers Squibb, Princeton, NJ, USA.
5. Larkin, J, Chiarion-Sileni, V, Gonzalez, R, et al. Combined nivolumab and ipilimumab or monotherapy in untreated melanoma. N Engl J Med 373 (2015), 23–34.
6. Robert, C, Schachter, J, Long, GV, et al. Pembrolizumab versus ipilimumab in advanced melanoma. N Engl J Med 372 (2015), 2521–2532.
7. Schachter J, Robert C, Long GV, et al. Pembrolizumab (pembro) vs ipilimumab (ipi) in Patients with ipilimumab-naive advanced melanoma: updated efficacy and safety of the phase 3 KEYNOTE-006 study. Poster presented at the Society for Melanoma Research 2015 Congress; November 18–21, 2015; San Francisco, California, USA.
8. Hochberg, Y, A sharper Bonferroni procedure for multiple tests of significance. Biometrika 75 (1988), 800–802.
9. Cox, DR, Regression models and life tables. J Royal Stat Soc 34 (1972), 187–220.
10. Miettinen, O, Nurminen, M, Comparative analysis of two rates. Stat Med 4 (1985), 213–226.
11. Hodi, FS, O'Day, SJ, McDermott, DF, et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med 363 (2010), 711–723.
12. O'Day, SJ, Maio, M, Chiarion-Sileni, V, et al. Efficacy and safety of ipilimumab monotherapy in patients with pretreated advanced melanoma: a multicenter single-arm phase II study. Ann Oncol 21 (2010), 1712–1717.
13. Farolfi, A, Ridolfi, L, Guidoboni, M, et al. Ipilimumab in advanced melanoma: reports of long-lasting responses. Mel Res 22 (2012), 263–270.
14. Callahan, MK, Postow, MA, Wolchok, JD, Immunomodulatory therapy for melanoma: ipilimumab and beyond. Clin Dermatol 31 (2013), 191–199.
15. Schadendorf, D, Hodi, FS, Robert, C, et al. Pooled analysis of long-term survival data from phase II and phase III trials of ipilimumab in unresectable or metastatic melanoma. J Clin Oncol 33 (2015), 1889–1894.
16. Robert, C, Ribas, A, Hamid, O, et al. Three-year overall survival for patients with advanced melanoma treated with pembrolizumab in KEYNOTE-001. J Clin Oncol, 34, 2016 abstr 9503.
17. Larkin, J, Chiarion-Sileni, V, Gonzalez, R, Overall survival results from a phase III trial of nivolumab combined with ipilimumab in treatment-naïve patients with advanced melanoma (CheckMate-067), 2017, American Association of Cancer Research, Washington, DC, USA April 1–5, 2017. Abstract CT075.
18. Long, GV, Atkinson, V, Cebon, JS, et al. Pembrolizumab (pembro) plus ipilimumab (ipi) for advanced melanoma: results of the KEYNOTE-029 expansion cohort. J Clin Oncol, 34(suppl), 2016 abstr 9506.
19. Postow, MA, Chesney, J, Pavlick, AC, et al. Nivolumab and ipilimumab versus ipilimumab in untreated melanoma. N Engl J Med 372 (2015), 2006–2017.
20. Hodi, FS, Chesney, J, Pavlick, AC, et al. Combined nivolumab and ipilimumab versus ipilimumab alone in patients with advanced melanoma: 2-year overall survival outcomes in a multicentre, randomised, controlled, phase 2 trial. Lancet Oncol 17 (2016), 1558–1568.
21. Sznol, M, Kluger, HM, Callahan, MK, et al. Survival, response duration, and activity by BRAF mutation (MT) status of nivolumab (NIVO, anti-PD-1, BMS-936558, ONO-4538) and ipilimumab (IPI) concurrent therapy in advanced melanoma (MEL). J Clin Oncol, 32(suppl), 2014 abstr LBA 9003.
22. Gangadhar, TC, Hamid, O, Smith, DC, et al. Preliminary results from a phase I/II study of epacadostat (incb024360) in combination with pembrolizumab in patients with selected adbanced cancers. J Immunother Cancer, 3(suppl), 2015, 07.
23. Hamid O, Gadjewski TF, Smith DC, et al. Preliminary data from a phase I/II study of epacadostat (INCB024360) in combination with pembrolizumab in patients with advanced/metastatic melanoma. Presented at: 12th International Congress of the Society for Melanoma Research; November 18–21, 2015; San Francisco, CA.
24. Gangadhar TC, Hamid O, Smith DC, et al. Epacadostat plus pembrolizumab in patients with advanced melanoma and select solid tumors: Updated phase 1 results from ECHO-202/KEYNOTE-037. European Society for Medical Oncology Congress; Copenhagen, Denmark; Oct 7–11, 2016.
25. Long GV, Drummer R, Ribas A, et al. Efficacy analysis of MASTERKEY-265 phase 1b study of talimogene laherparepvec (T-VEC) and pembrolizumab (pembro) for unresectable stage IIIB-IV melanoma. J Clin Oncol 34: 6-3-2016.
26. Long GV, Drummer R, Ribas A, et al. Safety data from the phase 1b part of the MASTERKEY-265 study combining talimogene laherparepvec (T-VEC) and pembrolizumab for unresectable stage IIIB-IV melanoma. Presented at: 2015 European Cancer Congress; September 25-29; Vienna, Austria. Abstract LBA24.
27. V600-mutant advanced melanoma treated with vemurafenib. N Engl J Med 366 (2012), 707–714.
28. Aya, F, Fernandez-Martinez, A, Gaba, L, et al. Sequential treatment with immunotherapy and BRAF inhibitors in BRAF-mutant advanced melanoma. Clinical Translations in Oncology 19 (2017), 119–124.
29. Ackerman, A, Klein, O, McDermott, DF, et al. Outcomes of patients with metastatic melanoma treated with immunotherapy prior to or after BRAF inhibitors. Cancer, 2014.
30. V600 mutant melanoma: anti-PD-1 before and after BRAF inhibition. J Immunother 40 (2017), 31–35.
31. Postow, MA, Managing immune checkpoint-blocking antibody side effects. Am Soc Clin Oncol Educ Book 2015 (2015), 76–83.
32. Kahler, KC, Hassel, JC, Heinzerling, L, Loquai, C, Mossner, R, Ugurel, S, Zimmer, L, Gutzmer, R, Management of side effects of immune checkpoint blockade by anti-CTLA-4 and anti-PD-1 antibodies in metastatic melanoma. J Dtsch Dermato Ges 14 (2016), 662–681.
33. Naidoo, J, Page, DB, Li, BT, Connell, LC, Schindler, K, Lacouture, ME, Postow, MA, Wolchok, JD, Toxicities of the Anti-PD-1 and Anti-PD-L1 Immune Checkpoint Antibodies. Ann Oncol 26 (2015), 2375–2391.
34. Spain, L, Diem, S, Larkin, J, Management of toxicities of immune checkpoint inhibitors. Cancer Treat Rev 44 (2016), 51–60.