This phase Ib study (ClinicalTrials.gov, number NCT01656642 ) evaluated the safety and anti-tumor activity of combining atezolizumab (anti-PD-L1) with vemurafenib (BRAF inhibitor), or cobimetinib (MEK inhibitor) + vemurafenib, in patients with BRAF<sup>V600</sup>-mutated metastatic melanoma.
Immune checkpoint inhibitors including anti-CTLA-4 and anti-PD-1/PD-L1 antibodies are yielding impressive responses in intracranial manifestations of metastatic melanoma and NSCLC.
Association of combined PD-L1 expression and tumour-infiltrating lymphocyte features with survival and treatment outcomes in patients with metastatic melanoma.
Immunotherapy delivered a new therapeutic option to the oncologist: Ipilimumab (anti-CTLA-4), Nivolumab and Pembrolizumab (anti-PD1), and Atezolizumab (anti-PD-L1) increase overall survival and show a better safety profile compared to chemotherapy in patients with metastatic melanoma, lung, renal cancer among others.
We studied the formalin-fixed paraffin-embedded tumor samples of 36 patients with metastatic melanoma using PD-L1 immunohistochemistry (IHC) and PD-L1/chromosome 9 fluorescent in situ hybridization (FISH).
Another example is related to the administration of immune checkpoint inhibitors/ICIs (anti-CTLA-4 antibodies, anti-PD-1/PD-L1 antibodies), which are successfully used in metastatic melanoma.
Immunomagnetic targeting isolated melanoma CTCs in up to 87.5% of stage IV melanoma patient blood samples and 3 8.6% of these had some PD-L1 expressing CTCs.
In particular, antibody-based therapies that block the PD-1/PD-L1 checkpoint inhibitory pathway have achieved an increased overall response rate in metastatic melanoma, yet durable response rates are reported only around 15%.
The clinical benefit of immunotherapy was supported by convincing evidence in the following settings: anti-PD-1/PD-L1 monoclonal antibody (mAb) therapy for treating advanced melanoma and non-small cell lung cancer (NSCLC), the combination of rituximab and chemotherapy for treating chronic lymphocytic leukemia and B-cell non-Hodgkin's lymphoma, adoptive cell immunotherapy for NSCLC, and the combination of interferon α and chemotherapy for metastatic melanoma.
Novel immunotherapies including antibodies to programmed death ligand 1 (PD-1) and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) have become common therapies for neoplasms including metastatic melanoma and non-small cell lung cancer (NSCLC).
The field of tumor immunology has faced many complex challenges over the last century, but the approval of immune checkpoint inhibitors (anti-cytotoxic T-lymphocyte-associated protein 4 [CTLA4] and anti-programmed cell death-1 [PD-1]/PD-ligand 1 [PD-L1]) and talimogene laherparepvec (T-VEC) for the treatment of metastatic melanoma have awakened a new wave of interest in cancer immunotherapy.
Immune checkpoint inhibitors targeting either the programmed death (PD)-1 receptor or its ligand PD-L1 were first approved by the Food and Drug Administration (FDA) for the management of metastatic melanoma in 2011.
Given this, the objective of the current study was to ascertain concordance of somatic mutations in BRAF/NRAS/TERT and immunohistochemical PD-L1 and CD8 in matched primary cutaneous and metastatic melanoma.
Mucous Membrane Pemphigoid, Bullous Pemphigoid, and Anti-programmed Death-1/ Programmed Death-Ligand 1: A Case Report of an Elderly Woman With Mucous Membrane Pemphigoid Developing After Pembrolizumab Therapy for Metastatic Melanoma and Review of the Literature.
At present, there are two main classes of therapies acting with a certain efficiency on metastatic melanoma: immune check point inhibitors (anti-PD1/PDL1) and targeted therapy such as Vemurafenib.
Recent successes in the development of new therapies for metastatic melanoma, such as mitogen-activated protein kinase pathway inhibitors, anticytotoxic T lymphocyte-associated antigen-4, and programmed cell death protein 1/programmed cell death ligand 1 (PD-L1) pathway-blocking antibodies, as well as combination strategies, all yielded promising results, changing the continually evolving landscape of therapeutic options for patients with melanoma.
The advent of immune checkpoint inhibitors anti-PD-1/PD-L1 has delivered new and effective treatment options with proven clinical benefits for patients affected by metastatic melanoma.
Preliminary results from clinical trials involving triple combination therapy with BRAF-MEK inhibitors and anti-PD-L1 antibodies appear promising and may indicate a new strategy to treat patients with BRAF-mutated metastatic melanoma.