Ciardiello Davide, Boscolo Bielo Luca, Napolitano Stefania, Cioli Eleonora, Latiano Tiziana Pia, De Stefano Alfonso, Tamburini Emiliano, Ramundo Matteo, Bordonaro Roberto, Russo Alessia Erika, Pisconti Salvatore, Nisi Claudia, Lotesoriere Claudio, Vallarelli Simona, Lonardi Sara, Barruca Viola, Cremolini Chiara, Tortora Giampaolo, Tagliaferri Pierosandro, Pietrantonio Filippo, Rosati Gerardo, Lucenti Antonio, Scartozzi Mario, Brunetti Oronzo, Zampino Maria Giulia, Zaniboni Alberto, Berardi Rossana, Paoletti Giancarlo, Febbraro Antonio, Martinelli Erika, Troiani Teresa, Normanno Nicola, Parente Paola, Fazio Nicola, Curigliano Giuseppe, De Vita Ferdinando, Avallone Antonio, Maiello Evaristo, Ciardiello Fortunato, Martini Giulia
Division of Gastrointestinal Medical Oncology and Neuroendocrine Tumors, European Institute of Oncology, IEO, IRCCS, Milan, Italy.
Division of New Drugs and Early Drug Development for Innovative Therapies, European Institute of Oncology, IRCCS, Milan, Italy; Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy.
Eur J Cancer. 2025 Aug 26;226:115642. doi: 10.1016/j.ejca.2025.115642. Epub 2025 Jul 12.
We investigated the role of integrating tissue biopsy (TBx)- and liquid biopsy (LBx)-comprehensive genomic profiling (CGP) to predict the activity of FOLFIRI plus cetuximab.
The CAPRI-2 GOIM study is a non-randomized phase 2 study evaluating a biomarker-driven anti-EGFR treatment in three lines of therapy in patients with RAS/BRAF wild type metastatic colorectal cancer. At baseline, TBx and LBx were analyzed using the FoundationOne CDx platform. Analysis of overall response rate (ORR) and median progression free survival (mPFS) according to molecular profiles were performed.
Overall, 156 patients were evaluable for tumor response and had matched tissue and plasma-based CGP. Negatively hyper-selected patients by both TBx- and LBx-CGP showed higher ORR (79.6 % versus 44.2 %, P < 0.001) and mPFS compared to mutated cases (12.4 months versus 7.4 months, P < 0.001). Eight and 12 cases harbored mutations detected by TBx and LBx-CGP only, respectively. Compared to discordant cases (n = 20), concordant cases (n = 23) showed a trend for lower ORR (39.1 % versus 50.0 %, P = 0.5) and shorter mPFS (3.94 versus 11.50 months, P = 0.02). Patients with alterations detected only by TBx-CGP had significantly lower circulating tumor DNA (ctDNA) tumor fraction (TF) compared to concordant cases (1.7 % versus 23.0 %; P = 0.01). Using a ctDNA TF threshold ≥ 10 % nearly all (19 of 20) TBx detected pathogenic variants (PV) were also identified by LBx-CGP. In eight cases detected by LBx only, mPFS was 8.24 months.
In cases with high TF LBx-CGP predicts efficacy of anti-EGFR therapy, while for TF< 10 % TBx-CGP provides additional data on PVs that could affect treatment efficacy.
我们研究了整合组织活检（TBx）和液体活检（LBx）的综合基因组分析（CGP）在预测FOLFIRI联合西妥昔单抗活性方面的作用。
CAPRI-2 GOIM研究是一项非随机的2期研究，评估生物标志物驱动的抗EGFR治疗在RAS/BRAF野生型转移性结直肠癌患者三线治疗中的应用。在基线时，使用FoundationOne CDx平台对TBx和LBx进行分析。根据分子特征对总缓解率（ORR）和中位无进展生存期（mPFS）进行分析。
总体而言，156例患者可评估肿瘤反应，并具有匹配的基于组织和血浆的CGP。与突变病例相比，经TBx和LBx-CGP均进行阴性超选择的患者显示出更高的ORR（79.6%对44.2%，P<0.001）和mPFS（12.4个月对7.4个月，P<0.001）。分别有8例和12例仅通过TBx和LBx-CGP检测到突变。与不一致病例（n=20）相比，一致病例（n=23）显示出ORR较低（39.1%对50.0%，P=0.5）和mPFS较短（3.94对11.50个月，P=0.02）的趋势。仅通过TBx-CGP检测到改变的患者与一致病例相比，循环肿瘤DNA（ctDNA）肿瘤分数（TF）显著更低（1.7%对23.0%；P=0.01）。使用ctDNA TF阈值≥10%时，几乎所有（20例中的19例）TBx检测到的致病变异（PV）也被LBx-CGP识别。在仅通过LBx检测到的8例病例中，mPFS为8.24个月。
在TF高的病例中，LBx-CGP可预测抗EGFR治疗的疗效，而对于TF<10%的情况，TBx-CGP可提供可能影响治疗疗效的PV的额外数据。
