Combined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma.
- Larkin J From the Department of Medical Oncology, Royal Marsden Hospital, London (J.L.), and South West Wales Cancer Institute, Singleton Hospital, Swansea (J.W.) - both in the United Kingdom; Melanoma Oncology Unit, Veneto Region Oncology Research Institute, Padua (V.C.-S.), Oncology of Melanoma Unit, European Institute of Oncology, Milan (P.F.F.), University Hospital of Siena, Siena (M.M.), and Istituto Nazionale Tumori Fondazione Pascale, Naples (P.A.A.) - all in Italy; Division of Medical Oncology, University of Colorado, Denver, Denver (R.G.); Aix-Marseille University, Hôpital de La Timone, Assitance Publique-Hôpitaux de Marseille, Marseille (J.J.G.), and Hôtel Dieu Place Alexis Ricordeau, Nantes (B.D.) - both in France; Baylor Charles A. Sammons Cancer Center, Dallas (C.L.C.); Departments of Internal Medicine and Dermatology, University of Michigan, Ann Arbor (C.D.L.); Department of Dermatology, University of Essen, Essen, Germany (D.S.); University of Zürich Hospital, Zurich, Switzerland (R.D.); Cross Cancer Institute, Edmonton, AB, Canada (M. Smylie); Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland (P.R.); Tasman Oncology Research, Southport Gold Coast, QLD (A.H.), and Westmead and Blacktown Hospitals (M.S.C.) and Melanoma Institute Australia (M.S.C., G.V.L.), University of Sydney, and the Mater Hospital (G.V.L.), Sydney, and Peter MacCallum Cancer Centre and University of Melbourne, Melbourne, VIC (G.A.M.) - all in Australia; Division of Medical Oncology, the Netherlands Cancer Institute, Amsterdam (J.B.H.); Servicio de Oncología Médica, Hospital General Universitario Gregorio Marañón, Madrid (I.M.-R.); Ludwig Center, Memorial Sloan Kettering Cancer Center (M.K.C., M.A.P., J.D.W.) and Weill Cornell Medical College (M.K.C., M.A.P., J.D.W.) - both in New York; Huntsman Cancer Institute, University of Utah, Salt Lake City (K.G.); Yale Cancer Center, Smilow Cancer Hospital of the Yale-New Haven Hospital, Yale University Sc
- Chiarion-Sileni V
- Gonzalez R
- Grob JJ
- Cowey CL
- Lao CD
- Schadendorf D
- Dummer R
- Smylie M
- Rutkowski P
- Ferrucci PF
- Hill A
- Wagstaff J
- Carlino MS
- Haanen JB
- Maio M
- Marquez-Rodas I
- McArthur GA
- Ascierto PA
- Long GV
- Callahan MK
- Postow MA
- Grossmann K
- Sznol M
- Dreno B
- Bastholt L
- Yang A
- Rollin LM
- Horak C
- Hodi FS
- Wolchok JD
- 2015-06-02
Published in:
- The New England journal of medicine. - 2015
Adult
Aged
Aged, 80 and over
Antibodies, Monoclonal
Antineoplastic Agents
Antineoplastic Combined Chemotherapy Protocols
Disease-Free Survival
Double-Blind Method
Female
Humans
Intention to Treat Analysis
Ipilimumab
Male
Melanoma
Middle Aged
Nivolumab
Skin Neoplasms
Tumor Burden
English
BACKGROUND
Nivolumab (a programmed death 1 [PD-1] checkpoint inhibitor) and ipilimumab (a cytotoxic T-lymphocyte-associated antigen 4 [CTLA-4] checkpoint inhibitor) have been shown to have complementary activity in metastatic melanoma. In this randomized, double-blind, phase 3 study, nivolumab alone or nivolumab plus ipilimumab was compared with ipilimumab alone in patients with metastatic melanoma.
METHODS
We assigned, in a 1:1:1 ratio, 945 previously untreated patients with unresectable stage III or IV melanoma to nivolumab alone, nivolumab plus ipilimumab, or ipilimumab alone. Progression-free survival and overall survival were coprimary end points. Results regarding progression-free survival are presented here.
RESULTS
The median progression-free survival was 11.5 months (95% confidence interval [CI], 8.9 to 16.7) with nivolumab plus ipilimumab, as compared with 2.9 months (95% CI, 2.8 to 3.4) with ipilimumab (hazard ratio for death or disease progression, 0.42; 99.5% CI, 0.31 to 0.57; P<0.001), and 6.9 months (95% CI, 4.3 to 9.5) with nivolumab (hazard ratio for the comparison with ipilimumab, 0.57; 99.5% CI, 0.43 to 0.76; P<0.001). In patients with tumors positive for the PD-1 ligand (PD-L1), the median progression-free survival was 14.0 months in the nivolumab-plus-ipilimumab group and in the nivolumab group, but in patients with PD-L1-negative tumors, progression-free survival was longer with the combination therapy than with nivolumab alone (11.2 months [95% CI, 8.0 to not reached] vs. 5.3 months [95% CI, 2.8 to 7.1]). Treatment-related adverse events of grade 3 or 4 occurred in 16.3% of the patients in the nivolumab group, 55.0% of those in the nivolumab-plus-ipilimumab group, and 27.3% of those in the ipilimumab group.
CONCLUSIONS
Among previously untreated patients with metastatic melanoma, nivolumab alone or combined with ipilimumab resulted in significantly longer progression-free survival than ipilimumab alone. In patients with PD-L1-negative tumors, the combination of PD-1 and CTLA-4 blockade was more effective than either agent alone. (Funded by Bristol-Myers Squibb; CheckMate 067 ClinicalTrials.gov number, NCT01844505.).
Nivolumab (a programmed death 1 [PD-1] checkpoint inhibitor) and ipilimumab (a cytotoxic T-lymphocyte-associated antigen 4 [CTLA-4] checkpoint inhibitor) have been shown to have complementary activity in metastatic melanoma. In this randomized, double-blind, phase 3 study, nivolumab alone or nivolumab plus ipilimumab was compared with ipilimumab alone in patients with metastatic melanoma.
METHODS
We assigned, in a 1:1:1 ratio, 945 previously untreated patients with unresectable stage III or IV melanoma to nivolumab alone, nivolumab plus ipilimumab, or ipilimumab alone. Progression-free survival and overall survival were coprimary end points. Results regarding progression-free survival are presented here.
RESULTS
The median progression-free survival was 11.5 months (95% confidence interval [CI], 8.9 to 16.7) with nivolumab plus ipilimumab, as compared with 2.9 months (95% CI, 2.8 to 3.4) with ipilimumab (hazard ratio for death or disease progression, 0.42; 99.5% CI, 0.31 to 0.57; P<0.001), and 6.9 months (95% CI, 4.3 to 9.5) with nivolumab (hazard ratio for the comparison with ipilimumab, 0.57; 99.5% CI, 0.43 to 0.76; P<0.001). In patients with tumors positive for the PD-1 ligand (PD-L1), the median progression-free survival was 14.0 months in the nivolumab-plus-ipilimumab group and in the nivolumab group, but in patients with PD-L1-negative tumors, progression-free survival was longer with the combination therapy than with nivolumab alone (11.2 months [95% CI, 8.0 to not reached] vs. 5.3 months [95% CI, 2.8 to 7.1]). Treatment-related adverse events of grade 3 or 4 occurred in 16.3% of the patients in the nivolumab group, 55.0% of those in the nivolumab-plus-ipilimumab group, and 27.3% of those in the ipilimumab group.
CONCLUSIONS
Among previously untreated patients with metastatic melanoma, nivolumab alone or combined with ipilimumab resulted in significantly longer progression-free survival than ipilimumab alone. In patients with PD-L1-negative tumors, the combination of PD-1 and CTLA-4 blockade was more effective than either agent alone. (Funded by Bristol-Myers Squibb; CheckMate 067 ClinicalTrials.gov number, NCT01844505.).
- Language
-
- English
- Open access status
- green
- Identifiers
-
- DOI 10.1056/NEJMoa1504030
- PMID 26027431
- Persistent URL
- https://folia.unifr.ch/global/documents/66273
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