Circulating Thymidine Kinase Activity Predicts Survival and Optimal Treatment Sequencing in BRAF-Mutated Metastatic Melanoma in the SECOMBIT Trial.
Hildur Helgadottir, Mariaelena Capone, Laura Ridolfi et al.
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In 30 seconds
This randomized phase II trial biomarker analysis evaluated circulating thymidine kinase activity (TKa) in patients with BRAF V600-mutated metastatic melanoma receiving targeted therapy (TT), immune checkpoint inhibition (ICI), or a short TT induction “sandwich” sequence. Patients were grouped by median baseline TKa. At 5 years, overall survival was 70.7% in the TKa-low group versus 36.9% in the TKa-high group (P < 0.001); total progression-free survival was also longer with low TKa. Among patients with high TKa, outcomes were improved with the sandwich strategy compared with other sequences.
Key findings
- At 5 years, overall survival was 70.7% in TKa-low versus 36.9% in TKa-high patients (P < 0.001).
- Five-year total progression-free survival was 60.8% versus 35% in TKa-low and TKa-high patients, respectively (P = 0.004).
- TKa-high patients had improved outcomes with short-term TT induction before ICI, followed by TT, compared with other treatment sequences.
- TKa increased early in most patients receiving ICI and rose at disease progression.
Why it matters
Baseline TKa was associated with substantial differences in survival, while the reported sequencing results suggest that TKa may help identify patients who could benefit from a particular treatment sequence. Changes during therapy may also provide information about disease course. Together, these findings support further evaluation of a blood-based marker for risk stratification and monitoring in metastatic BRAF-mutated melanoma.
What to keep in mind
This is a biomarker analysis within a phase II trial, and the reported subgroup and treatment-sequence findings do not establish TKa-guided sequencing as beneficial in a prospective biomarker-directed comparison.