Using a blood test to track thymidine kinase activity may help determine optimal first-line treatment for patients with BRAF V600–mutated metastatic melanoma, according to findings published in Clinical Cancer Research.
"The results suggest that thymidine kinase activity may help identify which patients could benefit from different treatment strategies. At the same time, further studies are needed before the method can be introduced into clinical practice," said first study author Hildur Helgadottir, MD, PhD, Docent in the Department of Oncology-Pathology, Karolinska Institutet.
Study Methods
Researchers looked at the activity of circulating thymidine kinase to determine outcome and treatment sequencing in patients with BRAF V600–mutated metastatic melanoma. Patients came from the randomized phase II SECOMBIT trial, which looked at the use of sequential immunotherapy and targeted therapy in patients with BRAF V600–mutated metastatic melanoma.
The trial showed that survival was improved in most patients with sequential treatment of immunotherapy followed by targeted therapy of BRAF/MEK inhibition. However, a few patients still required initial tumor control with BRAF/MEK inhibition before receiving immunotherapy.
In this analysis, serum thymidine kinase activity was analyzed at baseline and during treatment. Patients were stratified by their mean baseline thymidine kinase activity levels of low (n = 41) vs high (n = 40). Survival outcomes were compared in three strategies by treatment sequence of targeted therapy followed by immune checkpoint inhibition (arm A), immune checkpoint inhibition followed by BRAF/MEK inhibition (arm B), and a "sandwich" strategy of short-term targeted therapy induction then immune checkpoint inhibition followed by BRAF/MEK inhibition again.
Key Findings
At 5 years, the first progression-free survival rate was 43.3% in patients with low baseline thymidine kinase activity levels vs 27.5% in patients with high activity (P = .062). Total progression-free survival rates were 60.8% and 35% in patients with low and high activity, respectively (P = .004), and overall survival rates were 70.4% and 36.9% (P < .001).
In arms A and B, patients with low baseline thymidine kinase activity had significantly prolonged total progression-free survival and overall survival compared with those with high thymidine kinase activity. Patients with high thymidine kinase activity, on the other hand, showed improved outcomes in arm C.
Additionally, longitudinal analyses showed an early increase in thymidine kinase activity in patients receiving immunotherapy, and levels increased at disease progression.
The study authors concluded that circulating thymidine kinase activity could be used as a clinically actionable biomarker for stratifying risk, sequencing treatment, and monitoring disease during treatment.
DISCLOSURES: The study was funded by, among others, the Swedish Cancer Society, Bristol Myers Squibb and Array Biopharma/Pfizer. For full disclosures of the study authors, visit aacrjournals.org.
