The concepts of rechallenge and retreatment in melanoma: A proposal for consensus definitions

TY - JOUR

T1 - The concepts of rechallenge and retreatment in melanoma: A proposal for consensus definitions

AU - Gebhardt, Christoffer

AU - Ascierto, Paolo

AU - Atkinson, Victoria

AU - Corrie, Pippa

AU - Dummer, Reinhard

AU - Schadendorf, Dirk

N1 - Copyright © 2020 Elsevier Ltd. All rights reserved.

PY - 2020/10

Y1 - 2020/10

N2 - Patients with BRAF-mutant melanoma commonly develop resistance to BRAF inhibitor and MEK inhibitor (BRAF/MEKi) treatment, resulting in disease recurrence or progression. Repeated treatment after a break or an intervening therapy may provide clinical benefit. To ensure a common understanding when discussing the treatment of BRAF-mutant melanoma, we propose consensus definitions for retreatment and rechallenge. 'Retreatment' should be defined as 'repeated treatment with the same therapeutic class following relapse after adjuvant treatment has ended.' Retreatment may be an option for patients with unresectable or metastatic disease who have completed prior adjuvant therapy or discontinued adjuvant therapy early due to toxicity or patients with locoregional recurrence after adjuvant treatment who subsequently underwent resection. 'Rechallenge' should be defined as 'repeated treatment with the same therapeutic class following disease progression in patients who had clinical benefit with prior treatment for unresectable or metastatic disease.' Rechallenge may be an option for patients who had disease progression after an initial response and received an alternative intervening treatment or patients with unresectable or metastatic melanoma who had a treatment break after responding to BRAF/MEKi therapy. Clinical benefits may be possible with repeated BRAF/MEKi treatment because of the role of the MAPK pathway in melanoma oncogenesis and resistance mechanisms specific to BRAF/MEKi, which are discussed in this article. The concepts of retreatment and rechallenge may also be relevant for treatment with immune checkpoint inhibitors in patients with melanoma. Use of consistent terminology will help to stimulate and align further research in this area.

AB - Patients with BRAF-mutant melanoma commonly develop resistance to BRAF inhibitor and MEK inhibitor (BRAF/MEKi) treatment, resulting in disease recurrence or progression. Repeated treatment after a break or an intervening therapy may provide clinical benefit. To ensure a common understanding when discussing the treatment of BRAF-mutant melanoma, we propose consensus definitions for retreatment and rechallenge. 'Retreatment' should be defined as 'repeated treatment with the same therapeutic class following relapse after adjuvant treatment has ended.' Retreatment may be an option for patients with unresectable or metastatic disease who have completed prior adjuvant therapy or discontinued adjuvant therapy early due to toxicity or patients with locoregional recurrence after adjuvant treatment who subsequently underwent resection. 'Rechallenge' should be defined as 'repeated treatment with the same therapeutic class following disease progression in patients who had clinical benefit with prior treatment for unresectable or metastatic disease.' Rechallenge may be an option for patients who had disease progression after an initial response and received an alternative intervening treatment or patients with unresectable or metastatic melanoma who had a treatment break after responding to BRAF/MEKi therapy. Clinical benefits may be possible with repeated BRAF/MEKi treatment because of the role of the MAPK pathway in melanoma oncogenesis and resistance mechanisms specific to BRAF/MEKi, which are discussed in this article. The concepts of retreatment and rechallenge may also be relevant for treatment with immune checkpoint inhibitors in patients with melanoma. Use of consistent terminology will help to stimulate and align further research in this area.

KW - Consensus

KW - Drug Resistance, Neoplasm

KW - Humans

KW - MAP Kinase Signaling System/physiology

KW - Melanoma/drug therapy

KW - Mitogen-Activated Protein Kinase Kinases/antagonists & inhibitors

KW - Mutation

KW - Proto-Oncogene Proteins B-raf/antagonists & inhibitors

KW - Retreatment

KW - Skin Neoplasms/drug therapy

U2 - 10.1016/j.ejca.2020.07.016

DO - 10.1016/j.ejca.2020.07.016

M3 - SCORING: Journal article

C2 - 32861208

VL - 138

SP - 68

EP - 76

JO - EUR J CANCER

JF - EUR J CANCER

SN - 0959-8049

ER -