This analysis provides long-term follow-up in patients with BRAF wild-type advanced melanoma receiving first-line therapy based on anti-programmed cell death 1 receptor inhibitors.
To understand how tumors escape anti-tumor immunity, we investigated tumor-associated T-cell repertoires of patients with advanced melanoma and after blockade of the cytotoxic T-lymphocyte-associated protein 4 (CTLA4) or programmed cell death 1 (PD-1).
Programmed cell death protein 1 (PD-1) blocking monoclonal antibodies improve the overall survival of patients with advanced melanoma but the optimal duration of treatment has not been established.
Since the approval of the first immune checkpoint (CTLA-4) inhibitor ipilimumab in 2011 and programmed death-1 (PD-1) blocking monoclonal antibodies pembrolizumab and nivolumab thereafter, an increasing proportion of patients with unresectable advanced melanoma achieved long-term overall survival.
This review focuses on pre-clinical studies and early to phase III clinical trials to discuss the development of combined therapy based on BRAF inhibitors for BRAF-mutant advanced melanoma, as well as mechanisms of resistance to BRAF inhibitors.
Panniculitis and vitiligo occurring during BRAF and MEK inhibitors combination in advanced melanoma patients: Potential predictive role of treatment efficacy.
This study found that hybrid capture-based next-generation sequencing can detect BRAF alterations in samples from a significant fraction of patients with advanced melanoma with prior negative BRAF results.
Reactivation of functionally-impaired anticancer T cells by programmed cell death protein 1 (PD-1) and programmed cell death receptor ligand-1 (PD-L1)-blocking antibodies shows prominent therapeutic benefit in advanced melanoma and patients with non-small cell lung cancer.
Panniculitis and vitiligo occurring during BRAF and MEK inhibitors combination in advanced melanoma patients: Potential predictive role of treatment efficacy.
Future strategies for the treatment of advanced melanoma include novel combination therapies using BRAF/MEK inhibitors and immune checkpoints inhibitors or histone deacetylase inhibitors.
The findings highlight the efficacy of combination PD-1 with CTLA-4 inhibitors and combination BRAF with MEK inhibitors in the treatment of advanced melanoma.
No difference was recorded in OS by brain metastases (log-rank P = .22) or BRAF mutation status (log-rank P = .90).These findings support effectiveness of pembrolizumab in the real-world clinical setting and provide important insights into patient characteristics and outcomes associated with pembrolizumab therapy for a heterogeneous patient population with advanced melanoma, including patients who would not be eligible for clinical trials.
The findings highlight the efficacy of combination PD-1 with CTLA-4 inhibitors and combination BRAF with MEK inhibitors in the treatment of advanced melanoma.
Combination immune checkpoint blockade with concurrent administration of the anti-ctla4 antibody ipilimumab and the anti-PD-1 antibody nivolumab has demonstrated impressive responses in patients with advanced melanoma and other diseases.
Glembatumumab vedotin had modest activity and an acceptable safety profile in patients with advanced melanoma who were refractory to checkpoint inhibitors and MEK/BRAF inhibition.