BRAF inhibitor cessation prior to disease progression in metastatic melanoma: Long-term outcomes

Joanna Lee, Tasnia Ahmed, Andrea Maurichi, Lorenzo Di Guardo, Anna M. Stagno, Lydia Warburton, Amelia. M. Taylor, Elisabeth Livingstone, Saba Rehman, Adnan Khattak, Katharina C. Kahler, Vito Vanella, Victoria Atkinson, Michael Millward, Dirk Schadendorf, Douglas B. Johnson, Paolo A. Ascierto, Axel Hauschild, Serigne N. Lo, Georgina V. LongAlexander M. Menzies, Matteo S. Carlino

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

Background
BRAF mutant melanoma treated with BRAF f MEK inhibitor (targeted therapy) has a high response rate; however, most patients progress (PD). Some patients have durable response, but it is unknown whether treatment can be discontinued in these patients. We describe the recurrence risk, progression patterns, response to subsequent treatment, and survival of patients with advanced melanoma who ceased targeted therapy prior to PD.

Patients and methods
Ninety-four patients who ceased targeted therapy without progression were identified retrospectively from 11 centres: 45 were male; 81 V600E; 88 stage IV. Fifty-nine were treated with BRAF + MEK inhibitor, and 35 were treated with BRAF inhibitor alone. Median treatment duration was 29.6 months (range 0.36-77.9). At cessation, 67 were in complete response, 21 in partial response, and 2 stable disease.

Results
After median follow-up from cessation of 42.9 months (range 0.0-88.7), 36 (38%) progressed; median time to progression was 4.7 months (range 0.7-56.9); 30 (83%) were asymptomatic and 7 (19%) had new brain metastases. Progression rates did not differ by best response: 34% for complete response and 43% for partial response (P = 0.65). Treatment duration was strongly associated with risk of progression: Median treatment duration was 18.3 (range 0.85-65.7) months for those who progressed and 34.6 (range 0.36-77.9) months for those who did not (P = 0.0004). Twenty-two received further targeted therapy with 15 (68%) responses.

Conclusion
Risk of progression after cessation of targeted therapy is strongly associated with treatment duration. Response to retreatment with targeted therapy is high. 2022 Elsevier Ltd. All rights reserved.
Original languageEnglish
Pages (from-to)87-97
Number of pages11
JournalEuropean Journal of Cancer
Volume179
DOIs
Publication statusPublished - Jan 2023

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