Case Reports
17 June 2025
Early Access
Durable complete response in a patient with BRAF-mutated advanced melanoma with ocular and skin toxicities from BRAF/MEK targeted therapy after immune checkpoint inhibitor treatment: a case report
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All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
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Here we report the case of a woman suffering from advanced melanoma who developed severe toxicities with BRAF and MEK inhibitors (BRAFis, MEKis), given as second-line therapy after failure of immunotherapy, who achieved a complete and durable response lasting for over 5 years. Significant progress has been achieved in the treatment of advanced melanoma with immune checkpoint inhibitors (ICIs) and targeted therapies using BRAFis and MEKis. While these treatments improve survival, they also pose risks of severe toxicities. Notably, when targeted therapy follows immunotherapy, immune-mediated toxicities may emerge months later due to tumor microenvironment modulation. Despite these risks, both approaches offer a durable response in eligible patients. Further understanding is needed to determine how prior immunotherapy may influence subsequent toxicity risks of target therapy. Understanding these factors could optimize treatment strategies and improve patient outcomes.
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Citations
1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA Cancer J Clin 2019;69:7-34. DOI: https://doi.org/10.3322/caac.21551
2. Shah V, Panchal V, Shah A, et al. Immune checkpoint inhibitors in metastatic melanoma therapy (Review). Med Int (Lond) 2024;4:13. DOI: https://doi.org/10.3892/mi.2024.137
3. Moreira A, Heinzerling L, Bhardwaj N, Friedlander P. Current Melanoma Treatments: Where Do We Stand? Cancers (Basel) 2021;13:221. DOI: https://doi.org/10.3390/cancers13020221
4. Dummer R, Ascierto PA, Gogas HJ, et al. Encorafenib plus binimetinib versus vemurafenib or encorafenib in patients with BRAF-mutant melanoma (COLUMBUS): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol 2018;19:603-15. DOI: https://doi.org/10.1016/S1470-2045(18)30142-6
5. Welsh SJ, Corrie PG. Management of BRAF and MEK inhibitor toxicities in patients with metastatic melanoma. Ther Adv Med Oncol 2015;7:122-36. DOI: https://doi.org/10.1177/1758834014566428
6. Kakadia S, Yarlagadda N, Awad R, et al. Mechanisms of resistance to BRAF and MEK inhibitors and clinical update of US Food and Drug Administration-approved targeted therapy in advanced melanoma. Onco Targets Ther 2018;11:7095-07. DOI: https://doi.org/10.2147/OTT.S182721
7. Koya RC, Mok S, Otte N, et al. BRAF inhibitor vemurafenib improves the antitumor activity of adoptive cell immunotherapy. Cancer Res 2012;72:3928-37. DOI: https://doi.org/10.1158/0008-5472.CAN-11-2837
8. Su F, Viros A, Milagre C, et al. RAS mutations in cutaneous squamous-cell carcinomas in patients treated with BRAF inhibitors. N Engl J Med 2012;366:207-15. DOI: https://doi.org/10.1056/NEJMoa1105358
9. Pulluri B, Kumar A, Shaheen M, et al. Tumor microenvironment changes leading to resistance of immune checkpoint inhibitors in metastatic melanoma and strategies to overcome resistance. Pharmacol Res 2017;123:95-102. DOI: https://doi.org/10.1016/j.phrs.2017.07.006
10. Hu-Lieskovan S, Robert L, Homet Moreno B, Ribas A. Combining targeted therapy with immunotherapy in BRAF-mutant melanoma: promise and challenges. J Clin Oncol 2014;32:2248-54. DOI: https://doi.org/10.1200/JCO.2013.52.1377
11. Morgese F, Cognigni V, Scortichini L, et al. Potential immune related adverse events during dabrafenib and trametinib treatment: A case series of patients with BRAF V600E melanoma. Mol Clin Oncol 2022;18:2. DOI: https://doi.org/10.3892/mco.2022.2598
12. Livingstone E, Zimmer L, Vaubel J, Schadendorf D. BRAF, MEK and KIT inhibitors for melanoma: adverse events and their management. Chin Clin Oncol 2014;3:29.
13. Sinha R, Edmonds K, Newton-Bishop JA, et al. Cutaneous adverse events associated with vemurafenib in patients with metastatic melanoma: practical advice on diagnosis, prevention and management of the main treatment-related skin toxicities. Br J Dermatol 2012;167:987-94. DOI: https://doi.org/10.1111/bjd.12010
14. Renouf DJ, Velazquez-Martin JP, Simpson R, et al. Ocular toxicity of targeted therapies. J Clin Oncol 2012;30:3277-86. DOI: https://doi.org/10.1200/JCO.2011.41.5851
15. Ziogas DC, Konstantinou F, Bouros S, et al. Combining BRAF/MEK Inhibitors with Immunotherapy in the Treatment of Metastatic Melanoma. Am J Clin Dermatol 2021;22:301-14. DOI: https://doi.org/10.1007/s40257-021-00593-9
16. Grogan N, Swami U, Bossler AD, et al. Toxicities with targeted therapies after immunotherapy in metastatic melanoma. Melanoma Res 2018;28:600-4. DOI: https://doi.org/10.1097/CMR.0000000000000493
17. Lamiaux M, Scalbert C, Lepesant P, et al. Severe skin toxicity with organ damage under the combination of targeted therapy following immunotherapy in metastatic melanoma. Melanoma Res 2018;28:451-7. DOI: https://doi.org/10.1097/CMR.0000000000000472
18. Wyluda EJ, Cheng J, Schell TD, et al. Durable complete responses off all treatment in patients with metastatic malignant melanoma after sequential immunotherapy followed by a finite course of BRAF inhibitor therapy. Cancer Biol Ther 2015;16:662-70. DOI: https://doi.org/10.1080/15384047.2015.1026507
19. Cooper ZA, Juneja VR, Sage PT, et al. Response to BRAF inhibition in melanoma is enhanced when combined with immune checkpoint blockade. Cancer Immunol Res 2014;2:643-54. DOI: https://doi.org/10.1158/2326-6066.CIR-13-0215
20. Hermel DJ, Ott PA. Combining forces: the promise and peril of synergistic immune checkpoint blockade and targeted therapy in metastatic melanoma. Cancer Metastasis Rev 2017;36:43-50. Erratum in: Cancer Metastasis Rev 2017;36:51. DOI: https://doi.org/10.1007/s10555-017-9656-2
How to Cite
Durable complete response in a patient with BRAF-mutated advanced melanoma with ocular and skin toxicities from BRAF/MEK targeted therapy after immune checkpoint inhibitor treatment: a case report. (2025). Dermatology Reports. https://doi.org/10.4081/dr.2025.10324
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