PDF(Pubmed)
Abstract：
Metastatic pancreatic cancer (mPC) has a dismal prognosis. Herein, we conducted a prospective, multicentre, single-arm, phase II trial evaluating the efficacy and safety of penpulimab and anlotinib in combination with nab-paclitaxel/gemcitabine (PAAG) in patients with first-line mPC (NCT05493995). The primary endpoints included the objective response rate (ORR) and disease control rate (DCR), while secondary endpoints encompassed progression-free survival (PFS), overall survival (OS), and safety. In 66 patients analysed for efficacy, the best response, indicated by the ORR, was recorded at 50.0% (33/66) (95% CI, 37.4-62.6%), with 33 patients achieving partial response (PR). Notably, the DCR was 95.5% (63/66, 95% CI, 87.3-99.1%). The median PFS (mPFS) and OS (mOS) were 8.8 (95% CI, 8.1-11.6), and 13.7 (95% CI, 12.4 to not reached) months, respectively. Grade 3/4 treatment-related adverse events (TRAEs) were reported in 39.4% of patients (26/66). In prespecified exploratory analysis, patients with altered SWI/SNF complex had a poorer PFS. Additionally, low serum CA724 level, high T-cell recruitment, low Th17 cell recruitment, and high NK CD56dim cell scores at baseline were potential predicative biomarkers for more favourable efficacy. In conclusion, PAAG as a first-line therapy demonstrated tolerability with promising clinical efficacy for mPC. The biomolecular findings identified in this study possess the potential to guide the precise clinical application of the triple-combo regimen.
摘要：
转移性胰腺癌（mPC）预后不良。在这里，我们进行了一个前瞻性的，多中心,单臂,II期试验评估pepulimab和安洛替尼联合nab-紫杉醇/吉西他滨(PAAG)在一线mPC患者中的疗效和安全性(NCT05493995).主要终点包括客观缓解率（ORR）和疾病控制率（DCR）。而次要终点包括无进展生存期（PFS），总生存期（OS），和安全。在分析疗效的66例患者中，最好的回应,由ORR指示，记录为50.0%(33/66)(95%CI，37.4-62.6%)，33例患者达到部分缓解（PR）。值得注意的是,DCR为95.5％（63/66，95％CI，87.3-99.1％）。中位PFS(mPFS)和OS(mOS)为8.8(95%CI,8.1-11.6),和13.7个月(95%CI，12.4至未达到)，分别。39.4%的患者报告了3/4级治疗相关不良事件（TRAEs）（26/66）。在预先指定的探索性分析中，SWI/SNF复合物改变的患者PFS较差.此外,低血清CA724水平，高T细胞募集，低Th17细胞募集，基线时较高的NKCD56dim细胞评分是疗效更有利的潜在预测生物标志物.总之,PAAG作为一线治疗证明了mPC的耐受性和有希望的临床疗效。本研究中确定的生物分子发现具有指导三重组合方案的精确临床应用的潜力。
