Combined Therapy with Anti-PD1 and BRAF and/or MEK Inhibitor for Advanced Melanoma: A Multicenter Cohort Study

Despite significant progress in melanoma survival, therapeutic options are still needed in case of progression under immune checkpoint inhibitors (ICI), and resistance to targeted therapies (TT) in BRAF-mutated melanomas. This study aimed to assess the safety of combined ICI and TT as a rescue line...

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Bibliographic Details
Published in:Cancers 2020-06, Vol.12 (6), p.1666
Main Authors: Huynh, Sandra, Mortier, Laurent, Dutriaux, Caroline, Maubec, Eve, Boileau, Marie, Dereure, Olivier, Leccia, Marie-Therese, Arnault, Jean-Philippe, Brunet-Possenti, Florence, Aubin, Francois, Dreno, Brigitte, Beylot-Barry, Marie, Lebbe, Celeste, Lefevre, Wendy, Delyon, Julie
Format: Article
Language:English
Subjects:
Antigens
Apoptosis
Cancer
Clinical medicine
Clinical trials
Cohort analysis
Cytotoxicity
Dermatology
Diarrhea
Disease control
Fever
Human health and pathology
Immune checkpoint inhibitors
Immunology
Immunotherapy
Life Sciences
Medical prognosis
MEK inhibitors
Melanoma
Metastasis
Monoclonal antibodies
Patients
PD-1 protein
Pembrolizumab
Pharmaceutical sciences
Pharmacology
Response rates
Survival
Toxicity
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Summary:Despite significant progress in melanoma survival, therapeutic options are still needed in case of progression under immune checkpoint inhibitors (ICI), and resistance to targeted therapies (TT) in BRAF-mutated melanomas. This study aimed to assess the safety of combined ICI and TT as a rescue line in real-life clinical practice. We conducted a study within the prospective French multicentric MelBase cohort, including patients treated with a combination of anti-PD1 (pembrolizumab/nivolumab) and BRAF inhibitor (BRAFi: dabrafenib/vemurafenib) and/or MEK inhibitors (MEKi: trametinib/cobimetinib) for BRAF mutated or wild-type advanced melanoma. Fifty-nine patients were included: 30% received the triple combination, 34% an anti-PD1 and BRAFi, and 36% an anti-PD1 and MEKi. Grade 3–4 adverse events occurred in 12% of patients. Permanent discontinuation or dose reduction of one of the treatments for toxicity was reported in 14% and 7% of patients, respectively. In the BRAF wild-type subgroup, treatment with MEKi and anti-PD1 induced a tumor control rate of 83% and median progression-free survival of 7.1 months. The combination of anti-PD1 and BRAFi and/or MEKi was a safe rescue line for advanced melanoma patients previously treated with ICI/TT. The benefit of these combinations, specifically anti-PD1 and MEKi in BRAF wild-type melanoma patients, needs to be prospectively studied.
ISSN:2072-6694
2072-6694
DOI:10.3390/cancers12061666