Efficacy and safety of anti-PD-1 and anti-PD-1 combined with anti-CTLA-4 immunotherapy to advanced melanoma

Abstract

Background:Anti-PD-1 monoclonal antibodies, nivolumab and pembrolizumab, and anti-CTLA-4 antibody ipilimumab are being in clinic trials to treat melanoma. Here, we performed a meta-analysis to evaluate the efficacy and toxicity of them against advanced melanoma.Methods:Eleven reports from 6 randomized control trials on treating metastatic melanoma, which were divided into 3 subgroups, nivolumab/pembrolizumab versus chemotherapy, nivolumab versus ipilimumab, and nivolumab-plus-ipilimumab versus ipilimumab, were included and the meta-analysis was performed for each subgroup. The outcome measures were objective response rates (ORR), median progression free survival (PFS), 1-year overall survival rates (OS), and toxicity estimated by grade 3 to 4 adverse events.Results:For nivolumab/pembrolizumab versus chemotherapy, nivolumab versus ipilimumab, and nivolumab-plus-ipilimumab versus ipilimumab, the pooled risk ratios (RR) of the ORR were 3.43 (95% CI: 2.57–4.58), 2.51 (95% CI: 2.03–3.09), and 3.28 (95% CI: 2.58–4.17), respectively. The pooled HR of PFS were 0.42 (95% CI: 0.36–0.49), 0.58 (95% CI: 0.50–0.66), and 0.41 (95% CI: 0.30–0.52), respectively. The pooled RR of 1-year OS was 1.37 (95% CI: 1.08–1.74) and 1.54 (95% CI: 0.90–2.63) for nivolumab versus ipilimumab and nivolumab-plus-ipilimumab versus ipilimumab. These results suggested that anti-PD-1 monotherapy and nivolumab-plus-ipilimumab therapy had ORR and PFS benefit compared with the control group. Anti-PD-1 treatment increased 1-year OS for patients compared with ipililumab treatment. But there is no significantly difference on 1-year OS between the nivolumab-plus-ipilimumab treatment and the ipilimumab treatment group. The toxicity analysis showed that there is less risk of adverse events in the anti-PD-1 treatment group compared with the chemotherapy and ipilimumab group. Combining nivolumab with ipilimumab increased the risk for high-grade adverse events compared with ipilimumab alone but the adverse events were generally manageable.Conclusions:Anti-PD-1 monotherapy and nivolumab-plus-ipilimumab therapy improved ORR and prolonged PFS of patients with advanced melanoma and the adverse events are generally manageable. The therapy is indeed a promising approach for treatment of advanced melanoma.

Rheumatic Syndromes Associated With Immune Checkpoint Inhibitors: A Single‐Center Cohort of Sixty‐One Patients

“…There was 1 case of PMR flare and 3 cases of new-onset PMR-like syndrome (patients [5][6][7][8]. CTD included cases of diffuse systemic sclerosis-like syndrome and sicca syndrome (patients [9][10][11][12][13][14]. In all cases of necrotizing vasculitis and systemic sclerosis, skin biopsy supported the clinical diagnosis.…”

Melanoma of the Vagina: Case Report and Systematic Review of the Literature

“…Specifically, it is unclear if treatment strategies should follow current practice regarding female genital tract cancer or should be extrapolated from established strategies used for cutaneous melanomas (11,12). In addition, the clinical rationale of molecular tumor characterization of PMV regarding BRAF, KIT, or NRAS as well as the therapeutic value of immunotherapies and targeted therapies such as the monoclonal antibodies to the programmed cell death protein-1 (PD-1) nivolumab and pembrolizumab and the antibody to the cytotoxic Tlymphocyte-associated protein 4 (CTLA-4) ipilimumab has not been established for patients with PMV (13).…”

Primary amelanotic malignant melanoma of cervix masquerading as squamous cell carcinoma presenting with extensive metastases

“…Immunotherapy options including ipilimumab—the anti-CTLA-4 (cytotoxic T- lymphocyte-  associated protein-4) antibody, anti-PD-1, anti-PD-L1 inhibitors including pembrolizumab, nivolumab and combination therapy have shown promising results in the cases of metastatic melanoma as combination therapy and are under various evaluation in clinical trials; from the conclusion, a metanalysis anti-PD-1 monotherapy and nivolumab-plus-ipilimumab therapy prolonged progression-free survival and improved overall survival in patients with advanced melanoma has been observed and the adverse events are generally manageable. The therapy appears to be a promising approach for the treatment of advanced melanoma 20. The response rate and progression-free survival have been observed to be proportional to the tumour proportion score and immune proportion score of PD-L1 21.…”