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Review
. 2018 Jul 17:2018:6279871.
doi: 10.1155/2018/6279871. eCollection 2018.

Clinical and Molecular Characteristics Associated with Survival in Advanced Melanoma Treated with Checkpoint Inhibitors

Sunil Badami  1 , Sunil Upadhaya  1 , Ravi Kanth Velagapudi  1 , Pushyami Mikkilineni  2 , Ranju Kunwor  3 , Samer Al Hadidi  4 , Ghassan Bachuwa  1
Affiliations
Review

Clinical and Molecular Characteristics Associated with Survival in Advanced Melanoma Treated with Checkpoint Inhibitors

Sunil Badami et al. J Oncol. .

Abstract

Background: We performed meta-analysis to gather more evidence regarding clinical-molecular subgroups associated with better overall survival (OS) in advanced melanoma treated with checkpoint inhibitors.

Materials and methods: We performed a systematic search of PubMed, Scopus, Cochrane Library, and clinical trial.gov. Randomized clinical trials that compared a checkpoint inhibitor (nivolumab or pembrolizumab) with investigator choice chemotherapy or ipilimumab were included in our study. Hazard ratios (HR) and confidence interval (CI) were calculated for progression-free survival (PFS) and OS for each subgroup using generic inverse model along with the random effect method.

Results: A total of 6 clinical trials were eligible for the meta-analysis. OS was prolonged in wild BRAF subgroup (HR 0.65, 95% CI 0.49-0.85, p 0.002), Programmed cell death subgroup (PD-1+) (HR 0.57, 95% CI 0.41-0.80, p 0.001), and high lactate dehydrogenase (LDH) level subgroup (HR 0.60, 95% CI 0.38-0.95, p 0.03). Similarly, we found increased OS in eastern cooperative oncology group (ECOG) 1, males and age >65 years subgroups.

Conclusions: Checkpoint inhibitors significantly increased OS in patients with wild BRAF, positive PD-1, and high LDH. However, results should be interpreted keeping in mind associated significant heterogeneity. The results of this study should help in designing future clinical trials.

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Figures

Figure 1
Figure 1
PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) diagram of the review.
Figure 2
Figure 2
Forest plot for overall survival wild BRAF subgroup. CI: confidence interval; CM: CheckMate; KN: KeyNote; IV: inverse variance; SE: standard error.
Figure 3
Figure 3
Forest plot for overall survival mutated BRAF subgroup. CI: confidence interval; CM: CheckMate; KN: KeyNote; IV: inverse variance; SE: standard error.
Figure 4
Figure 4
Forest plot for overall survival PD1 positive subgroup. CI: confidence interval; CM: CheckMate; KN: KeyNote; IV: inverse variance; SE: standard error.
Figure 5
Figure 5
Forest plot for overall survival PD1 negative subgroup. CI: confidence interval; CM: CheckMate; KN: Keynote; IV: inverse variance; SE: standard error.
Figure 6
Figure 6
Overall survival in high lactate dehydrogenase (LDH) subgroup. CI: confidence interval; CM: CheckMate; KN: KeyNote; IV: inverse variance; SE: standard error.
Figure 7
Figure 7
Overall survival in normal lactate dehydrogenase (LDH) subgroup. CI: confidence interval; CM: CheckMate; KN: KeyNote; IV: inverse variance; SE: standard error.
See this image and copyright information in PMC

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