Pharmacological interventions for melanoma: Comparative analysis using bayesian meta-analysis

Abstract

We conducted a network meta-analysis in order to compare different strategies for managing melanoma patients. Electronic databases were searched for eligible randomized trials that compared different strategies in efficacy and tolerability. Five interventions were associated with a significant improvement in PFS over chemotherapy (all HR < 1): Ipilimumab, Tremelimumab, Nivolumab, Pembrolizumab 2 mg/kg and Ipilimumab + Nivolumab. Three interventions exhibited significantly improved OS results over chemotherapy (all HR < 1): Ipilimumab, Nivolumab and Ipilimumab + Chemotherapy. Four interventions were superior to chemotherapy in CR and PR (all OR > 1): Nivolumab, Pembrolizumab 10 mg/kg, Pembrolizumab 2 mg/kg and Ipilimumab + Nivolumab. However, the other seven interventions were associated with an increased risk of pruritus compared to chemotherapy (all OR > 1). Ipilimumab, Tremelimumab, Ipilimumab + Nivolumab and Ipilimumab + Chemotherapy might result in a higher risk of diarrhea compared to chemotherapy (all OR > 1). Immune checkpoint therapy or combined interventions might be more effective than chemotherapy for managing melanoma patients. However, chemotherapy appears to be more tolerable than these combined strategies with respect to adverse events.

Gastrointestinal Adverse Events with Combination of Checkpoint Inhibitors in Advanced Melanoma: A Systematic Review

“…The risk of any grade of diarrhea with the combination was examined in two network meta-analyses, which found a significantly higher risk with the combination when compared with ipilimumab monotherapy, nivolumab monotherapy, pembrolizumab monotherapy or chemotherapy [ 17 , 27 ]. However, a traditional meta-analysis found no significant difference between the ipilimumab-combination and ipilimumab monotherapy in the relative risk (RR) of grade 3–5 diarrhea (RR: 1.38; 95% CI: 0.85–2.25; I2 = 0%) or colitis (RR: 1.34; 95% CI: 0.47–3.80; I2 = 64%) [ 16 ].…”

“…However, a traditional meta-analysis found no significant difference between the ipilimumab-combination and ipilimumab monotherapy in the relative risk (RR) of grade 3–5 diarrhea (RR: 1.38; 95% CI: 0.85–2.25; I2 = 0%) or colitis (RR: 1.34; 95% CI: 0.47–3.80; I2 = 64%) [ 16 ]. Similarly, one of the two network meta-analyses found no significant difference in the risk of nausea with the combination compared with checkpoint inhibitor monotherapy, chemotherapy or ipilimumab plus chemotherapy [ 27 ].…”

“…Two network meta-analyses reported that the risk of developing diarrhea with combination therapy was higher than with chemotherapy or with monotherapy using ipilimumab, nivolumab or pembrolizumab [ 17 , 27 ]. Matching this pattern observed for risk of diarrhea, the incidence of diarrhea was also higher with combination treatment compared with ipilimumab or nivolumab monotherapy.…”