The author starts this module by showing the overall survival curves in patients with melanoma, treated with first-line therapies for metastatic disease in clinical trials and achieving long-term survival with immunotherapy and targeted therapies.
The author explains the role of BRAF V600 mutation in melanoma, the results in terms of response rate, progression-free and overall survival with anti-BRAF plus anti-MEK combination versus anti-BRAF monotherapy, as well as safety profile in pivotal clinical trials.
In the section dedicated to targeted therapy, the author details the results from the key immunotherapy studies and patient characteristics affecting immune surveillance. The answer to the question whether there is a patient subgroup where combination therapy may have greater clinical benefit is also illustrated with findings from clinical trials.
The next section is dedicated to the elaboration of efficacy and safety findings from the clinical trial of sequential treatment by immuno and targeted therapy and to the list of on-going clinical trials.
Despite the durable responses, there are still many patients with metastatic melanoma, who do not benefit from the treatment, therefore a part of the module, illustrated with findings from clinical trials, is dedicated to problems on how to overcome primary and acquired resistance.
The author illustrates the tumour-directed immuno-oncology, new emerging pathways for future combinations with anti-PD1(L1) compounds, as well as new emerging immuno-oncology pathways and novel compounds, which promise to improve anti-tumour immune responses, including combinations and possible biomarkers.
This module provides an excellent overview of the progress made in the management of patients with metastatic melanoma in recent years, elaborates on rapid advances made by intensive clinical research and makes the promise that “the best is yet to come”!
Paolo A. Ascierto has reported:
Honoraria for Consultant and/or Advisory role from: BMS, Roche Genentech, MSD, Novartis, Array, Merck Serono, Pierre Fabre, Incyte, Genmab, MedImmune, AstraZeneca, Sindax, Sun Pharma, Sanofi, Idera, Ultimovacs, Sandoz, Immunocore, 4SC, Alkermes, Italfarmaco, Nektar, Boehringer Ingelheim, Eisai, Regeneron, Daiichi Sankyo, Pfizer, Oncosec, Nouscom, Takis, Lunaphore, Seagen.
Travel support from MSD.
Funding to his Institution from BMS, Roche Genentech, Array, Sanofi.
Non-financial interests:
President of Fondazione Melanoma Onlus Italy (since 2010).
President of Campania Society of ImmunoTherapy of Cancer (SCITO) Italy (since 2014).
Member of Steering Committee of Society for Melanoma Research (SMR; since 2016).
Member of Board of Directors of Society for Immunotherapy of Cancer (SITC; Nov. 2017-Dec. 2020).
The author is also a Member of: ASCO, SITC, EORTC Melanoma Cooperative Group, AIOM, SMR.