Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2017 Jun;6(6):1143-1153.
doi: 10.1002/cam4.1001. Epub 2017 May 1.

A systematic review and network meta-analysis of immunotherapy and targeted therapy for advanced melanoma

Joao Paulo da Silveira Nogueira Lima  1 , Mina Georgieva  2 , Benjamin Haaland  2 , Gilberto de Lima Lopes  3
Affiliations

A systematic review and network meta-analysis of immunotherapy and targeted therapy for advanced melanoma

Joao Paulo da Silveira Nogueira Lima et al. Cancer Med. 2017 Jun.

Abstract

Immune and BRAF-targeted therapies have changed the therapeutic scenario of advanced melanoma, turning the clinical decision-making a challenging task. This Bayesian network meta-analysis assesses the role of immunotherapies and targeted therapies for advanced melanoma. We retrieved randomized controlled trials testing immune, BRAF- or MEK-targeted therapies for advanced melanoma from electronic databases. A Bayesian network model compared therapies using hazard ratio (HR) for overall survival (OS), progression-free survival (PFS), and odds ratio (OR) for response rate (RR), along with 95% credible intervals (95% CrI), and probabilities of drugs outperforming others. We assessed the impact of PD-L1 expression on immunotherapy efficacy. Sixteen studies evaluating eight therapies in 6849 patients were analyzed. For OS, BRAF-MEK combination and PD-1 single agent ranked similarly and outperformed all other treatments. For PFS, BRAF-MEK combination surpassed all other options, including CTLA-4-PD-1 dual blockade hazard ratio (HR: 0.56; 95% CrI: 0.33-0.97; probability better 96.2%), whereas BRAF single agent ranked close to CTLA-4-PD-1 blockade. For RR, BRAF-MEK combination was superior to all treatments including CTLA-4-PD-1 (OR: 2.78; 1.18-6.30; probability better 97.1%). No OS data were available for CTLA-4-PD-1 blockade at the time of systematic review, although PFS and RR results suggested that this combination could also bring meaningful benefit. PD-L1 expression, as presently defined, failed to inform patient selection to PD-1-based immunotherapy. BRAF-MEK combination seemed an optimal therapy for BRAF-mutated patients, whereas PD-1 inhibitors seemed optimal for BRAF wild-type patients. Longer follow-up is needed to ascertain the role of CTLA-4-PD-1 blockade. Immunotherapy biomarkers remain as an unmet need.

Keywords: BRAF; Bayesian; biomarker; immunotherapy; melanoma; meta-analysis.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Overall survival network meta‐analysis. HR, hazard ratio; CrI, credible interval; PrI, Predictive interval; BRAF +  BRAF‐mutated patients; BRAF‐: BRAF wild‐type patients.
Figure 2
Figure 2
Progression‐free survival network meta‐analysis. HR, hazard ratio; CrI, credible interval; PrI, Predictive interval; BRAF+BRAF‐mutated patients; BRAF‐ BRAF wild‐type patients.
Figure 3
Figure 3
Response rate network meta‐analysis. HR, hazard ratio; CrI, credible interval; PrI, Predictive interval; BRAF+BRAF‐mutated patients; BRAF‐:BRAF wild‐type patients.
See this image and copyright information in PMC

References

    1. Eggermont, A. M. , Spatz A., and Robert C.. 2014. Cutaneous melanoma. Lancet 383:816–827. - PubMed
    1. Eigentler, T. K. , Caroli U. M., Radny P., and Garbe C.. 2003. Palliative therapy of disseminated malignant melanoma: a systematic review of 41 randomised clinical trials. Lancet Oncol. 4:748–759. - PubMed
    1. Harriesa, M. , Malvehyb J., Lebbec C., Herond L., Amelioe J., Szabof Z., et al. 2016. Treatment patterns of advanced malignant melanoma (stage III‐IV) ‐ A review of current standards in Europe. Eur. J. Cancer 60:179–189. - PubMed
    1. Middleton, M. R. , Dalle S., Claveau J., et al. 2016. Real‐world treatment practice in patients with advanced melanoma in the era before ipilimumab: results from the IMAGE study. Cancer Med. 5:1436–1443. - PMC - PubMed
    1. Schadendorf, D. , Hodi F. S., Robert C., et al. 2015. Pooled analysis of long‐term survival data from phase II and phase III trials of ipilimumab in unresectable or metastatic melanoma. J. Clin. Oncol. 33:1889–1894. - PMC - PubMed

Publication types

Substances