The evaluation of immunotherapy and chemotherapy treatment on melanoma: a network meta-analysis

Abstract

Background: Melanoma is a highly malignant tumor that develops from a neural crest derivative called melanocytes. Chemotherapy is recommended for patients with stage III/IV melanoma. Immunomodulation has also been shown to effectively improve the survival rate of such patients. In the current study, we aimed to perform a network meta-analysis on the therapeutic value of chemotherapy and immunotherapy on melanoma.

Results: Twenty randomized controlled trials (RCTs) were enrolled in the study. Our Results indicated that ipilimumab + nivolumab had the highest response rate among all therapies, pembrolizumab also had a good efficacy with an excellent tolerance. Chemotherapy had a low response rate, high adverse effects and progressive diseases qualities, therefore it is not recommended as a preferred treatment for patients with advanced melanoma.

Methods: The Cochrane library, PubMed and Embase databases were searched for relevant articles. Results of the pair-wise meta-analysis were illustrated by odd ratios (ORs) and corresponding 95% confidence intervals (CIs). Network meta-analysis was performed using a random-effects model under Bayesian framework. Results were illustrated by cumulative ORs and corresponding 95% credible interval (CrIs). The probabilities and outcomes of each treatment were ranked and summarized using the surface under the cumulative ranking curve (SUCRA).

Conclusions: We recommend pembrolizumab as the preferred treatment due to its high efficacy and low adverse effects, combination of ipilimumab and nivolumab could be used in severe symptoms.

Keywords: chemotherapy; immunotherapy; melanoma; network meta-analysis.

Figure 1. Evidence network of eligible comparisons for complete response, partial response, stable & progressive disease and overall response rate in network meta-analysis

The width of the lines represents the cumulative number of trials for each comparison and the size of every node is proportional to the number of enrolled participants (sample size).

Figure 2. Evidence network of eligible comparisons for various adverse events in network meta-analysis

The width of the lines represents the cumulative number of trials for each comparison and the size of every node is proportional to the number of enrolled participants (sample size).

Figure 3. Forest plots for the correlations of the complete-response outcome of 10 interventions on melanoma

Figure 4. Forest plots for the correlations of the partial-response outcome of 10 interventions on melanoma

Figure 5. Forest plots for the correlations of the all-adverse-event outcome of 10 interventions on melanoma

Figure 6. Forest plots for the correlations of the fatigue outcome of 10 interventions on melanoma

Figure 7. Rankograms showing cumulative probability of each strategy having each specific rank (1–10) for clinical response

Ranking indicates the probability to be the best treatment, the second best, the third best and so on. Rank 1st is best and Rank 10th is worst.

Figure 8. Rankograms showing cumulative probability of each strategy having each specific rank (1–10) for adverse events

Ranking indicates the probability to be the best treatment, the second best, the third best and so on. Rank 1st is best and Rank 10th is worst.

Figure 9. Funnel plot for assessing publications bias of clinical response

A Chemotherapy; B Ipilimumab 3 mg/kg; C Ipilimumab 10 mg/kg; D Tremelimumab 10 mg/kg; E Tremelimumab 15 mg/kg; F Nivolumab 3 mg/kg; G Pembrolizumab 10 mg/kg; H Pembrolizumab 2 mg/kg; I Ipilimumab+Nivolumab; J Ipilimumab+Chemotherapy.

Figure 10. Funnel plot for assessing publications bias of adverse events

A Chemotherapy; B Ipilimumab 3 mg/kg; C Ipilimumab 10 mg/kg; D Tremelimumab 10 mg/kg; E Tremelimumab 15 mg/kg; F Nivolumab 3 mg/kg; G Pembrolizumab 10 mg/kg; H Pembrolizumab 2 mg/kg; I Ipilimumab+Nivolumab; J Ipilimumab+Chemotherapy.