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Published on: September 8, 2021
Combined BRAF-Targeted Therapy with Immunotherapy in BRAF-Mutated Advanced Melanoma Patients
Pier Francesco Ferrucci1, Marko Lens2, Emilia Cocorocchio3
1Tumor Biotherapy Unit, Department of Experimental Oncology, European Institute of Oncology IRCCS, Via Ripamonti 435, 20141, Milan, Italy. pier.ferrucci@ieo.it.
Purpose Of Review:
To review evidence on the efficacy and safety of combined BRAF-targeted therapy and immune checkpoint inhibitors in patients with BRAF-mutated metastatic melanoma.
Recent Findings:
Programmed death-1 pathway inhibitors administered with BRAF/MEK inhibitors showed promising anti-tumour activity in BRAF-mutated advanced melanoma and were investigated for safety and efficacy in three large international clinical trials. Although, in two out of those three randomized phase III studies, progression-free survival (PFS) did not reach statistical significance, results showed that duration of response (DOR) and overall survival (OS) were improved using combined therapy, sustaining the scientific rationale for its use at least in a subset of metastatic melanomas. However, the frequent occurrence of autoimmunity-induced toxicities should be considered since it is limiting the continuity and the wide application of these regimens. Novel treatment modalities combining targeted therapy with checkpoint inhibitors require further clinical investigation and elucidation of their effect on the immune system and cancer cell modulation.
Insights
Combined BRAF-targeted therapy and immune checkpoint inhibitors show promise for BRAF-mutated metastatic melanoma, improving survival but causing toxicities. Further research is needed for optimal use.
Area of Science:
- Oncology
- Immunology
- Pharmacology
Background:
- Metastatic melanoma with BRAF mutations presents a therapeutic challenge.
- Targeted therapies and immune checkpoint inhibitors are key treatment modalities.
Purpose of the Study:
- To review evidence on the efficacy and safety of combined BRAF-targeted therapy and immune checkpoint inhibitors.
- To assess outcomes in patients with BRAF-mutated metastatic melanoma.
Main Methods:
- Review of three large international randomized phase III clinical trials.
- Analysis of progression-free survival (PFS), duration of response (DOR), and overall survival (OS).
- Evaluation of safety and toxicity profiles, particularly autoimmunity-induced toxicities.
Main Results:
- Combined therapy demonstrated promising anti-tumour activity in BRAF-mutated advanced melanoma.
- While PFS did not reach statistical significance in two trials, DOR and OS were improved.
- Frequent occurrence of autoimmunity-induced toxicities was noted, limiting treatment application.
Conclusions:
- Combined BRAF-targeted therapy and immune checkpoint inhibitors offer a scientific rationale for treating a subset of metastatic melanomas.
- Further clinical investigation is required to understand effects on the immune system and cancer cells.
- Managing treatment-related toxicities is crucial for wider application of these combined regimens.
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