Effectiveness of immunotherapy versus BRAF/MEK inhibitors in treatment-naïve BRAF-mutant advanced melanoma: A single institution retrospective analysis.
Authors: Ahmed Mamoon , Abdullah Hafez M , Ali Mohammad , Morris Kahlen , Perinkulam Sathyanarayanan Swaminathan Perinkulam , Ali Lina , Gurumoorthy Aarabhi , Bleeker Jonathan 
Published: June 2022

e21515

Background: Skin cancer is the most common type of cancer in the US. Melanoma constitutes about 1% of all skin cancers, but it accounts for most of skin cancer related deaths. In 2017, 85,000 new cases of melanoma were reported while 8000 people died. BRAF is the gene encoding for B-Raf protein; a serine/threonine-protein kinase involved in cell growth and survival. Activating mutations in BRAF are present in approximately 50% of melanomas. Therapeutics in melanoma have been rapidly evolving. Currently, advanced melanoma with a mutation in the BRAF gene has two different modalities for first-line treatment; immunotherapy which mediates checkpoint inhibition versus targeted therapy with BRAF + MEK inhibitors. The aim of our study was to compare effectiveness of immunotherapy versus BRAF/MEK inhibitors as first line treatment for metastatic BRAF-mutant advanced melanoma. Methods: A retrospective study of all patients aged ≥ 18 years, diagnosed with metastatic melanoma at our center between 1/1/2011 and 05/30/2021 was carried out. Patients who had BRAF negative melanoma or other active malignancies were excluded. Our primary endpoint was difference in overall survival and progression-free survival between two treatment groups. Secondary endpoint was to compare baseline characteristics associated with treatment options. Results: A total of 308 patients were diagnosed with advanced melanoma during the study period. N = 106 (34%) were found to have BRAF mutation. Of these, 88 (83%) received single-agent or combination immunotherapy while 18 (17%) received BRAF/MEK inhibitors. In immunotherapy group, 13 (14.7%) patients received combination immunotherapy while 75 (85%) got single agent treatment. 60 (56.6%) were males. Median age was 61 (89-21) years. Mean BMI at presentation was 29.5 ± 6.8 kg while mean LDH was 407 U/L. Mean age in immunotherapy and BRAF/MEK inhibitor group was 59.5 and 54.4 years, respectively. Differences between immunotherapy and BRAF/MEK inhibitors groups were observed in duration (months) between initiation of treatment and progression of disease (10.3 vs 7.23), death at time of last follow-up (21% vs 63%), remission at time of last follow up (37% vs 16%), and progression at time of last follow up (38% vs 16%). At the time of analysis, the mean follow-up was 28 ± 23.7 months in the immunotherapy group and 24 ± 23.3 months in the BRAF/MEK inhibitor group. Overall, at a mean follow up of 27.3 ± 23.5 months, no significant difference was found between the two treatment groups in unadjusted models in terms of overall survival (p 0.67) and progression free survival (p 0.16). Conclusions: Patients receiving first-line immunotherapy showed no significant survival benefit versus those receiving BRAF/MEK inhibitor therapy. This contrasts with other studies showing survival benefits in patients receiving immunotherapy as first line agent.