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Immunotherapy. 2019 May;11(7):617-629. doi: 10.2217/imt-2018-0208. Epub 2019 Mar 11.

Comparative efficacy of combination immunotherapy and targeted therapy in the treatment of BRAF-mutant advanced melanoma: a matching-adjusted indirect comparison.

Author information

1
Georgetown Lombardi Comprehensive Cancer Center, Washington, DC 20057, USA.
2
Center for Immuno-Oncology Research, Cleveland Clinic, Cleveland, OH 44106, USA.
3
Evidera, Inc., San Francisco, CA 94111, USA.
4
Bristol-Myers Squibb, Princeton, NJ 08540, USA.
5
Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA.

Abstract

AIM:

Comparison of clinical outcomes of nivolumab + ipilimumab versus BRAF + MEK inhibitors (dabrafenib + trametinib or vemurafenib + cobimetinib) in BRAF-mutant advanced melanoma.

METHODS:

Matching-adjusted indirect comparisons were conducted between nivolumab + ipilimumab (CheckMate 067/069 studies) and BRAF + MEK inhibitors (COMBI-d, COMBI-v and coBRIM studies). Overall survival (OS), progression-free survival and objective response rates were assessed.

RESULTS:

After adjusting, nivolumab + ipilimumab showed improved OS versus dabrafenib + trametinib (hazard ratio [HR] = 0.64; 95% CI: 0.46-0.89) or vemurafenib + cobimetinib (HR = 0.56; 95% CI: 0.36-0.89); OS outcomes were similar at 1 year, with benefits emerging after 12 months; progression-free survival and objective response rates were similar. Grade 3/4 adverse events occurred in 54.1% with nivolumab + ipilimumab, 31.6% with dabrafenib + trametinib and 59.5% with vemurafenib + cobimetinib.

CONCLUSION:

Nivolumab + ipilimumab had significantly improved clinical outcomes versus BRAF + MEK inhibitors, with benefits increasing after longer follow-up. Ongoing randomized trials directly comparing these treatments are necessary to prospectively validate these findings.

KEYWORDS:

cobimetinib; comparative efficacy; dabrafenib; ipilimumab; matching-adjusted indirect comparison; nivolumab; trametinib; vemurafenib

PMID:
30852924
DOI:
10.2217/imt-2018-0208
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