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Updated: Mar 6, 2026
A Melanoma Patient-Derived Xenograft Model
Published on: May 20, 2019
Dabrafenib plus trametinib rechallenge in four melanoma patients who previously progressed on this combination
Aljosja Rogiers1, Pascal Wolter, Oliver Bechter
1aDepartment of General Medical Oncology, University Hospitals KU Leuven, Leuven bDepartment of Hematology and Medical Oncology, CHR East Belgium, Verviers, Belgium.
Abstract:
In unresectable or metastatic melanoma with a BRAF V600 mutation, combined BRAF/MEK targeted therapy improves clinical outcomes. Yet, disease progression because of acquired resistance occurs in the majority of patients. There is emerging evidence that resistance to BRAF-inhibitor-based targeted therapy can be reversible in some cases. We retrospectively analyzed four patients with BRAF-mutant stage IV cutaneous melanoma who were treated with dabrafenib plus trametinib and rechallenged with the same combination after previously experiencing progression. At initial treatment with dabrafenib plus trametinib, three patients achieved a partial response and one patient achieved a complete response. Progression-free survival varied from 9.9 to 24.3 (median 19.8) months. The targeted therapy-free interval ranged from 2.3 to 11.7 (median 8.8) months. At rechallenge, all four patients had a partial response, with progression-free survival ranging from 3.6 to 6.8 (median 5.2) months. Clinical benefit and a second radiological response can be obtained upon readministration of dabrafenib plus trametinib after previously acquiring resistance to this combination. A better understanding of the biological underpinnings of genomic and nongenomic mechanisms of resistance to BRAF-inhibitor-based targeted therapy is needed to identify patients who may benefit from this rechallenge approach.
Insights
Rechallenging melanoma patients with BRAF/MEK inhibitors after resistance can restore treatment effectiveness. This approach offers clinical benefit and radiological response in patients with BRAF-mutant melanoma.
Area of Science:
- Oncology
- Dermatology
- Pharmacology
Background:
- BRAF/MEK targeted therapy improves outcomes in unresectable or metastatic melanoma with BRAF V600 mutations.
- Acquired resistance limits the long-term efficacy of BRAF-inhibitor-based targeted therapy in most patients.
- Emerging evidence suggests that resistance to BRAF-inhibitor therapy may be reversible in certain cases.
Purpose of the Study:
- To evaluate the efficacy of rechallenging patients with BRAF-mutant stage IV cutaneous melanoma using dabrafenib plus trametinib after disease progression.
- To assess clinical benefit and radiological response in patients undergoing a second course of BRAF/MEK targeted therapy.
Main Methods:
- Retrospective analysis of four patients with BRAF-mutant stage IV cutaneous melanoma.
- Patients were treated with dabrafenib plus trametinib, experienced progression, and were subsequently rechallenged with the same combination therapy.
- Progression-free survival and response rates were analyzed for both initial treatment and rechallenge phases.
Main Results:
- Initial treatment with dabrafenib plus trametinib resulted in partial responses in three patients and a complete response in one patient.
- Median progression-free survival during initial treatment was 19.8 months.
- Upon rechallenge, all four patients achieved partial responses, with a median progression-free survival of 5.2 months.
Conclusions:
- Readministration of dabrafenib plus trametinib can achieve clinical benefit and a second radiological response in patients with BRAF-mutant melanoma who previously developed resistance.
- Further research into the mechanisms of resistance is needed to identify patients most likely to benefit from this rechallenge strategy.
- This study highlights the potential for overcoming acquired resistance to BRAF-inhibitor-based therapy in melanoma.
