Circulating Thymidine Kinase Activity Predicts Survival and Optimal Treatment Sequencing in BRAF-Mutated Metastatic Melanoma in the SECOMBIT Trial.

The purpose of this study was to evaluate circulating thymidine kinase activity (TKa), a blood-based marker of cellular proliferation, as a biomarker of outcome and treatment sequencing in patients enrolled in the randomized phase II SECOMBIT trial (NCT02631447).

本研究的目的是评估循环胸苷激酶活性（TKa），一种基于血液的细胞增殖标志物，作为随机II期SECOMBIT试验（NCT02631447）中入组患者的治疗结果和治疗序列的生物标志物。

patients_and_methods

Serum TKa was analyzed in samples from patients at baseline and during treatment.

在基线和治疗期间对患者的血清TKa进行了分析。

Patients were stratified by median baseline TKa, and survival outcomes were compared across three strategies for first- and second-line treatments: TT followed by ICI (arm A), ICI followed by TT (arm B), and a "sandwich" strategy with short-term TT induction prior ICI (arm C) followed by TT.

患者按基线TKa的中位数进行分层，并比较了三种一线和二线治疗策略的生存结果：先TT后ICI（A组），先ICI后TT（B组），以及先短期TT诱导后ICI（C组）再TT的“三明治”策略。

Results

In TKa-low (n = 41) versus TKa-high (n = 40) patients, the first progression-free survival(PFS) at 5 years was 43.3% versus 27.5% (P = 0.062), the total PFS was 60.8% versus 35% (P = 0.004), and overall survival(OS) was 70.7% versus 36.9% (P < 0.001), respectively.

在TKa低（n = 41）与TKa高（n = 40）患者中，5年内的第一次无进展生存期（PFS）分别为43.3%和27.5%（P = 0.062），总无进展生存期（PFS）分别为60.8%和35%（P = 0.004），总生存期（OS）分别为70.7%和36.9%（P < 0.001）。

TKa-low patients had, compared with TKa-high, significantly longer total PFS and OS in arms A and B.

与TKa高患者相比，TKa低患者在A组和B组中总无进展生存期（PFS）和总生存期（OS）显著更长。

Notably, TKa-high patients showed improved outcomes with the sandwich strategy compared with other sequences.

值得注意的是，TKa高患者在“三明治”策略下与其他序列相比显示出改善的结果。

Longitudinal analyses revealed an early TKa increase in the majority of patients receiving ICI and increasing TKa levels at disease progression.

纵向分析揭示了大多数接受ICI治疗的患者在早期TKa增加，以及在疾病进展时TKa水平上升。

Conclusions

These findings suggest that circulating TKa could serve as a clinically actionable biomarker for risk stratification, treatment sequencing, and on-treatment disease monitoring.

这些发现表明，循环中的TKa可以作为一种临床可操作的生物标志物，用于风险分层、治疗序列安排以及治疗过程中的疾病监测。