Perspectives in Melanoma: meeting report from the Melanoma Bridge (December 3rd\u20135th, 2020, Italy)

Thomas F. Gajewski,Michael A. Postow,Sergio A. Quezada,Magdalena Thurin,Michele W.l. Teng ,Roger S. Lo,Soldano Ferrone,Iman Osman,Christian U. Blank ,Giorgio Trinchieri,Marc S. Ernstoff,Patrick Hwu,Jason J. Luke,Paolo A. Ascierto,Michelle Krogsgaard,Claus Garbe,Igor Puzanov,Reinhard Dummer,Corrado Caracò ,Bart Neyns,Bernard A. Fox,Paweł Kaliński ,Alessandro Testori

doi:10.1186/s12967-021-02951-x

Abstract

Advances in immune checkpoint therapy and targeted therapy have led to improvement in overall survival for patients with advanced melanoma. Single agent checkpoint PD-1 blockade and combination with BRAF/MEK targeted therapy demonstrated benefit in overall survival (OS). Superior response rates have been demonstrated with combined PD-1/CTLA-4 blockade, with a significant OS benefit compared with single-agent PD-1 blockade. Despite the progress in diagnosis of melanocytic lesions, correct classification of patients, selection of appropriate adjuvant and systemic therapies, and prediction of response to therapy remain real challenges in melanoma. Improved understanding of the tumor microenvironment, tumor immunity and response to therapy has prompted extensive translational and clinical research in melanoma. Development of novel biomarker platforms may help to improve diagnostics and predictive accuracy for selection of patients for specific treatment. There is a growing evidence that genomic and immune features of pre-treatment tumor biopsies may correlate with response in patients with melanoma and other cancers but they have yet to be fully characterized and implemented clinically. Overall, the progress in melanoma therapeutics and translational research will help to optimize treatment regimens to overcome resistance and develop robust biomarkers to guide clinical decision-making. During the Melanoma Bridge meeting (December 3rd–5th, 2020, Italy) we reviewed the currently approved systemic and local therapies for advanced melanoma and discussed novel biomarker strategies and advances in precision medicine.

Highlights

The treatment of metastatic melanoma has undergone a dramatic transformation over the past decade with the advent of molecular targeted therapy and immunotherapy
Therapeutic approaches targeting mutated BRAF 600 mutations are Food and Drug Administration (FDA)approved drugs that have been developed as inhibitors of BRAF V600 mutations
Most patients who respond to immunotherapy have T cell-inflamed tumors, with activity of anti-programmed death 1 (PD-1) agents associated with a T cell inflamed signature at baseline across multiple cancers

Summary

Introduction

The treatment of metastatic melanoma has undergone a dramatic transformation over the past decade with the advent of molecular targeted therapy and immunotherapy. Reducing β-adrenergic receptor signaling through the use of the β-blocker propranolol facilitated conversion of tumors to an immunologically active TME and was associated with a significantly increased efficacy of anti-PD-1 checkpoint blockade [16]. The potential of β-blockers to improve response to checkpoint blockade has been further explored in a phase I trial of propranolol and pembrolizumab in combination in patients with locally advanced and metastatic melanoma [19].

Results

Conclusion