BRAF inhibitor cessation prior to disease progression in metastatic melanoma: long term outcomes.

J. Lee, T. Ahmed, A. Maurichi, L. Di Guardo, A.M. Stagno, L. Warburton, A. Taylor, E. Livingstone, S. Rehman, A. Khattak, K. Kahler, V. Vanella, V. Atkinson, M. Millward, D. Schadendorf, D.B. Johnson, P.A. Ascierto, A. Hauschild, S.N. Lo, G.V. Long, A.M. Menzies, M.S. Carlino. European Journal of Cancer, 2022, ISSN 0959-8049,


Background: BRAF mutant melanoma treated with BRAF+/-MEK inhibitor (targeted therapy) has a high response rate, however most patients progress (PD). Some patients have durable response, but it is unknown if 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, 35 BRAF inhibitor alone. Median treatment duration was 29.6 months (range 0.36-77.9). At cessation, 67 were in complete response (CR), 21 in partial response (PR), and 2 stable disease (SD).

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 CR 43% for PR (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). 22 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.