Clinical Trials Unit, Department of Oncology, University of Cambridge, Cambridge, UK.
Cancer Molecular Diagnostics Laboratory, Department of Oncology, University of Cambridge, Cambridge, UK.
Br J Cancer. 2023 May;128(9):1672-1680. doi: 10.1038/s41416-023-02170-9. Epub 2023 Feb 22.
Chemotherapy for metastatic pancreatic adenocarcinoma (PDAC) offers limited benefits, but survival outcomes vary. Reliable predictive response biomarkers to guide patient management are lacking.
Patient performance status, tumour burden (determined by the presence or absence of liver metastases), plasma protein biomarkers (CA19-9, albumin, C-reactive protein and neutrophils) and circulating tumour DNA (ctDNA) were assessed in 146 patients with metastatic PDAC prior to starting either concomitant or sequential nab-paclitaxel + gemcitabine chemotherapy in the SIEGE randomised prospective clinical trial, as well as during the first 8 weeks of treatment. Correlations were made with objective response, death within 1 year and overall survival (OS).
Initial poor patient performance status, presence of liver metastases and detectable KRAS ctDNA all correlated with worse OS after adjusting for the different biomarkers of interest. Objective response at 8 weeks also correlated with OS (P = 0.026). Plasma biomarkers measured during treatment and prior to the first response assessment identified ≥10% decrease in albumin at 4 weeks predicted for worse OS (HR 4.75, 95% CI 1.43-16.94, P = 0.012), while any association of longitudinal evaluation of KRAS ctDNA with OS was unclear (β = 0.024, P = 0.057).
Readily measurable patient variables can aid the prediction of outcomes from combination chemotherapy used to treat metastatic PDAC. The role of KRAS ctDNA as a tool to guide treatment warrants further exploration.
ISRCTN71070888; ClinialTrials.gov (NCT03529175).
转移性胰腺导管腺癌（PDAC）的化疗获益有限，但生存结果存在差异。目前缺乏可靠的预测反应生物标志物来指导患者管理。
在 SIEGE 随机前瞻性临床试验中，146 例转移性 PDAC 患者在开始联合或序贯纳武利尤单抗联合吉西他滨化疗之前，以及在治疗的前 8 周内，评估了患者的体能状态、肿瘤负荷（通过有无肝转移来确定）、血浆蛋白生物标志物（CA19-9、白蛋白、C 反应蛋白和中性粒细胞）和循环肿瘤 DNA（ctDNA）。并将这些因素与客观缓解、1 年内死亡和总生存期（OS）进行了相关性分析。
初始较差的患者体能状态、存在肝转移和可检测到的 KRAS ctDNA 在调整了感兴趣的不同生物标志物后，均与 OS 较差相关。8 周时的客观缓解与 OS 也相关（P=0.026）。治疗期间和首次反应评估前测量的血浆生物标志物发现，第 4 周白蛋白下降≥10%预示着 OS 更差（HR 4.75，95%CI 1.43-16.94，P=0.012），而 KRAS ctDNA 的纵向评估与 OS 的任何关联尚不清楚（β=0.024，P=0.057）。
可测量的患者变量可以帮助预测用于治疗转移性 PDAC 的联合化疗的结果。KRAS ctDNA 作为指导治疗的工具的作用值得进一步探索。
ISRCTN71070888；ClinicalTrials.gov（NCT03529175）。
