Combined nivolumab and ipilimumab or monotherapy in untreated melanoma Journal Article
| Authors: | Larkin, J.; Chiarion-Sileni, V.; Gonzalez, R.; Grob, J. J.; Cowey, C. L.; Lao, C. D.; Schadendorf, D.; Dummer, R.; Smylie, M.; Rutkowski, P.; Ferrucci, P. F.; Hill, A.; Wagstaff, J.; Carlino, M. S.; Haanen, J. B.; Maio, M.; Marquez-Rodas, I.; McArthur, G. A.; Ascierto, P. A.; Long, G. V.; Callahan, M. K.; Postow, M. A.; Grossmann, K.; Sznol, M.; Dreno, B.; Bastholt, L.; Yang, A.; Rollin, L. M.; Horak, C.; Hodi, F. S.; Wolchok, J. D. |
| Article Title: | Combined nivolumab and ipilimumab or monotherapy in untreated melanoma |
| Abstract: | 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.) |
| Keywords: | survival; mutation; braf; trial; vemurafenib; plus dacarbazine |
| Journal Title: | New England Journal of Medicine |
| Volume: | 373 |
| Issue: | 1 |
| ISSN: | 0028-4793 |
| Publisher: | Massachusetts Medical Society |
| Date Published: | 2015-07-02 |
| Start Page: | 23 |
| End Page: | 34 |
| Language: | English |
| ACCESSION: | WOS:000357218700005 |
| DOI: | 10.1056/NEJMoa1504030 |
| PROVIDER: | wos |
| PUBMED: | 26027431 |
| PMCID: | PMC5698905 |
| Notes: | Article -- Source: Wos |
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