PO.CL05.07 · 临床研究

循环胸苷激酶活性（TKa）作为转移性非小细胞肺癌（NSCLC）的预测性和动态生物标志物：Immunoblood研究

Circulating thymidine kinase activity (TKa) as a predictive and dynamic biomarker in the metastatic non-small cell lung cancer (NSCLC): Immunoblood study

海报缩略图：循环胸苷激酶活性（TKa）作为转移性非小细胞肺癌（NSCLC）的预测性和动态生物标志物：Immunoblood研究

编号 7753 展板 13 时间 4/22 09:00–12:00 区域 Section 42 主讲 Mattias Bergqvist, BS

分会场 Immune Response to Therapies

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作者与单位 Authors & Affiliations

Maristella Giammaruco¹, Lorenza Landi², Mattias Bergqvist³, Gabriele Minuti², Silvia Carpano¹, Francesca Fusco¹, Martina Brandi¹, Fabiana Letizia Cecere¹, Vincenzo Pio Di Noia¹, Livia Tosetto¹, Andrea Torchia¹, Corrado Orciuolo¹, Daniele Marinelli¹, Grisel Maver Militello¹, Diana Giannarelli⁴, Federico Cappuzzo¹

¹Medical Oncology 2, IRCCS Regina Elena National Cancer Institute, Rome, Italy,²Clinical Trials Unit: Phase 1 and Precision Medicine, IRCCS Regina Elena National Cancer Institute, Rome, Italy,³Biovica International AB, Uppsala, Sweden,⁴Epidemiology and Biostatistics, Gemelli University Hospital Foundation, IRCCS, Rome, Italy

摘要 Abstract

中文摘要

引言：尽管免疫检查点抑制剂（ICIs）在转移性NSCLC治疗中取得了重大进展，但用于预测哪些患者将从治疗中获益以及监测早期治疗反应的可靠生物标志物仍然有限。胸苷激酶是DNA合成中的一种基础酶，其活性反映肿瘤细胞增殖和肿瘤侵袭性。本研究（NCT06823401）首次评估接受免疫治疗（IT）或化疗-免疫治疗（CHT-IT）的NSCLC患者血浆TKa水平。研究目的是确定基线TKa水平能否预测IT的疗效，以及治疗早期TKa水平的变化能否反映治疗反应，从而支持TKa作为患者治疗选择和早期疗效评估的微创生物标志物。TKa评估细胞增殖的能力有望反映和预测IT成功激活T细胞及疗效持久。方法：94例转移性NSCLC患者（男性50例，女性44例）在基线（治疗前）和第二个治疗周期采集血浆样本，其中93例接受一线全身治疗。使用经FDA批准并具CE标志的DiviTum® TKa检测法（Biovica，瑞典）测定循环TKa，数值以DiviTum活性单位（DuA）报告。分析在对临床结局设盲的情况下进行。评估TKa与反应率（RR）、无进展生存（PFS）、总生存（OS）的关系，并将其与包括PD-L1表达在内的其他生物标志物进行相关性分析。结果：65例患者（70%）接受一线CHT-IT，28例患者（30%）单独接受IT。PD-L1表达 <1% 者37例（40%），1-49% 者17例（18%），≥50% 者34例（36%），未知者6例（6%）。基线TKa中位水平为203 DuA。低TKa组（<203 DuA）和高TKa组的RR分别为52%和32%（p = 0.80），而低TKa组的mPFS未达到，高TKa组为7.3个月（p = 0.13）。两组的1年OS率相似（69.9% vs 62.4%，p = 0.34）。使用326 DuA的TKa临界值，我们观察到mPFS存在统计学显著差异；低TKa组（65例）为13.8个月，高TKa组（23例）为3.3个月（p = 0.004）。1年OS率分别为65.6% vs 53.3%（p = 0.18）。关于单独接受IT和接受CHT-IT患者的进一步数据将在会议上呈现。结论：我们的研究显示，在接受一线单独IT或联合CHT治疗的晚期NSCLC中，高血浆TKa水平可能与较短的PFS和OS相关，支持其在指导治疗选择方面的潜在作用。需要进一步研究以验证TKa在该情境下的预后和预测价值。

查看英文原文 English abstract

Introduction: Despite major advances with immune checkpoint inhibitors (ICIs) in treatment of metastatic NSCLC, reliable biomarkers to predict who will benefit from therapy and monitor early treatment response remain limited. Thymidine kinase is an enzyme fundamental in the DNA synthesis, its activity reflects tumor cell proliferation and tumor aggressiveness. This study (NCT06823401) is the first to evaluate plasma TKa levels in NSCLC patients receiving immunotherapy (IT) or chemotherapy-IT (CHT-IT). The objectives were to determine whether baseline TKa levels can predict efficacy of IT and if early on-treatment changes in TKa levels reflect treatment response, thereby supporting TKa as a minimally invasive biomarker for patient therapy selection and early efficacy assessment. The capacity of TKa to evaluate cell proliferation is expected to reflect and predict successful T-cell activation of IT and prolonged efficacy. Methods: 94 patients (50 males, 44 females) with metastatic NSCLC, had plasma samples collected at baseline (pre-treatment) and at second treatment cycle of whom 93 received first-line systemic therapy. Circulating TKa was measured using the FDA cleared and CE marked DiviTum ® TKa assay (Biovica, Sweden), with values reported in DiviTum units of activity (DuA). Analysis was performed blinded to clinical outcomes. TKa was evaluated for its association with response rate (RR), progression-free survival (PFS), overall survival (OS) and was also correlated to other biomarkers, including PD-L1 expression. Results: 65 pts (70%) received first-line CHT-IT, while 28 pts (30%) received IT alone. PD-L1 expression was <1% in 37 pts (40%), 1-49% in 17 pts (18%), ≥50% in 34 pts (36%), and unknown in 6 pts (6%). The median baseline TKa level was 203 DuA. The RR in the low (<203 DuA) and high-TKa group was 52% and 32% respectively (p = 0.80) while the mPFS was not reached in the low TKa group versus 7.3 mos in high TKa group (p = 0.13). The 1-year OS rate was similar between the two groups (69.9% vs 62.4%, p = 0.34). Using a TKa cutoff of 326 DuA, we observed a statistically significant difference in mPFS; 13.8 months in the low-TKa group (65 pts) versus 3.3 months in the high-TKa group (23 pts) (p = 0.004). The 1-year OS rate was 65.6% vs 53.3%, respectively (p = 0.18). Further data on patients treated with IT alone and with CHT-IT will be presented at the meeting. Conclusions: Our study shows a possible association between high plasma TKa levels and shorter PFS and OS in advanced NSCLC treated with first-line IT alone or combined with CHT, supporting the potential role in guiding treatment choice. Further studies are needed to validate the prognostic and predictive value of TKa in this setting.

利益披露 Disclosure

M. Giammaruco, None. L. Landi, Pfizer Other, Fees for membership of an advisory board or lectures. Astra Zeneca Other, Fees for membership of an advisory board or lectures. Novartis Other, Fees for membership of an advisory board or lectures. Roche Other, Fees for membership of an advisory board or lectures. BMS Other, Fees for membership of an advisory board or lectures. MSD Other, Fees for membership of an advisory board or lectures. Lilly Other, Fees for membership of an advisory board or lectures. Amgen Other, Fees for membership of an advisory board or lectures. Abbvie Other, Fees for membership of an advisory board or lectures. ThermoFisher Other, Fees for membership of an advisory board or lectures. J&J Other, Fees for membership of an advisory board or lectures. Nuvalent Other, Fees for membership of an advisory board or lectures. M. Bergqvist, Biovica Employment. G. Minuti, Astra Zeneca Other, Fees for membership of an advisory board or lectures. Roche Other, Fees for membership of an advisory board or lectures. BMS Other, Fees for membership of an advisory board or lectures. Gilead Other, Fees for membership of an advisory board or lectures. Novartis Other, Fees for membership of an advisory board or lectures. Sanofi Other, Fees for membership of an advisory board or lectures. Amgen Other, Fees for membership of an advisory board or lectures. MSD Other, Fees for membership of an advisory board or lectures. J%J Other, Fees for membership of an advisory board or lectures. Daiichi Sankyo Fees for membership of an advisory board or lectures. Pharma Mar Other, Fees for membership of an advisory board or lectures. S. Carpano, None.. F. Fusco, None.. M. Brandi, None.. F. Cecere, None. V. Di Noia, Astra Zeneca Other, speaker fees and grant consultancies. MSD Other, speaker fees and grant consultancies. BMS Other, speaker fees and grant consultancies. Boheringher Ingelheim Other, speaker fees and grant consultancies. Istituto Gentili Other, speaker fees and grant consultancies. Leopharm Other, speaker fees and grant consultancies. Regeneron Other, speaker fees and grant consultancies. Roche Travel. J&J. Travel. L. Tosetto, None.. A. Torchia, None.. C. Orciuolo, None.. D. Marinelli, None.. G. Maver Militello, None.. D. Giannarelli, None. F. Cappuzzo, Roche Other, Fees for membership of an advisory board or lectures. Astra Zeneca Other, Fees for membership of an advisory board or lectures. BMS Other, Fees for membership of an advisory board or lectures. Pfizer Other, Fees for membership of an advisory board or lectures. Takeda Other, Fees for membership of an advisory board or lectures. Lilly Other, Fees for membership of an advisory board or lectures. Bayer Other, Fees for membership of an advisory board or lectures. Amgen Other, Fees for membership of an advisory board or lectures. Sanofi Other, Fees for membership of an advisory board or lectures. Pharma Mar Other, Fees for membership of an advisory board or lectures. Novocure Other, Fees for membership of an advisory board or lectures. Mirati Other, Fees for membership of an advisory board or lectures. Galecto Other, Fees for membership of an advisory board or lectures. OSE Other, Fees for membership of an advisory board or lectures. Illumina Other, Fees for membership of an advisory board or lectures. Biontech Other, Fees for membership of an advisory board or lectures. Pierre Fabbre Other, Fees for membership of an advisory board or lectures. MSD Other, Fees for membership of an advisory board or lectures.

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