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Liquid Biopsy and Radiological Response Predict Outcomes Following Discontinuation of Targeted Therapy in Patients with BRAF Mutated Melanoma. | LitMetric

AI Article Synopsis

  • This study examines the outcomes of patients with metastatic melanoma who discontinued BRAF-targeted therapy due to cumulative toxicity after achieving a complete or long-lasting partial response.
  • A total of 24 patients were reviewed, revealing that after treatment stopped, 70.8% maintained progression-free survival for 12 months, and 58.3% for 24 months.
  • The research suggests that liquid biopsy could improve monitoring for patients with sustained sensitivity to treatment, especially since those with complete responses and undetectable circulating tumor DNA had better outcomes.

Article Abstract

Background: Outcomes of patients with metastatic melanoma discontinuing BRAF-targeted therapy for cumulative toxicity after sustained response are unknown.

Materials And Methods: This retrospective case series analysis conducted at a single Cancer Center in Italy included patients with BRAF mutated metastatic melanoma treated with a BRAF inhibitor as a single agent or in combination with a MEK inhibitor between June 1, 2011 and January 1, 2020 and interrupted treatment due to cumulative toxicity after achieving complete response (CR) or long-lasting partial response (PR; i.e. >12 months).

Results: We included 24 patients with a median treatment duration of 59.4 months (95% confidence interval [CI], 55.4-63.4; range, 12-88). CR and PR were achieved in 71% and 29% of patients, respectively. At a median follow-up after treatment discontinuation of 37.8 months (95% CI, 33.7-41.9), the 12-month progression-free survival after discontinuation (dPFS) rate was 70.8% (95% CI 54.8-91.6) and 24-month dPFS rate was 58.3% (95% CI, 41.6-81.8). Baseline patient and tumor characteristics as well as treatment duration and best response did not significantly impact on dPFS. Patients with CR and negative circulating tumor DNA (ctDNA) at time of discontinuation had a significantly improved dPFS compared with patients with either radiological residual disease or ctDNA positivity (p = .007). No patient in CR with undetectable ctDNA experienced progression.

Conclusion: The risk of progression is high even in patients with sustained sensitivity to BRAF/MEK inhibitors. Integration of liquid biopsy in clinical trials investigating the optimal management of patients with sustained sensitivity to BRAF/MEK inhibitors is warranted.

Implications For Practice: Outcomes of patients with metastatic melanoma discontinuing BRAF-targeted therapy for cumulative toxicity are unknown. This study analyzed patients with sustained responses (median treatment duration 59.4 months). Twelve- and 24-month progression-free survival following discontinuation were 70.8% and 58.3%, respectively. Complete response and negative circulating tumor DNA at time of discontinuation are promising prognostic biomarkers in this setting.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8649022PMC
http://dx.doi.org/10.1002/onco.13926DOI Listing

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