Comprehensive genomic profiling by liquid biopsy portrays metastatic colorectal cancer mutational landscape to predict antitumor efficacy of FOLFIRI plus cetuximab in the CAPRI-2 GOIM trial

被引：4

作者：

Ciardiello, D. ^{[1
]}

Bielo, L. B. ^{[2
,3
]}

Napolitano, S. ^{[4
]}

Latiano, T. P. ^{[5
]}

De Stefano, A. ^{[6
]}

Tamburini, E. ^{[7
]}

Toma, I. ^{[7
]}

Bordonaro, R. ^{[8
]}

Russo, A. E. ^{[8
]}

Pisconti, S. ^{[9
]}

Nisi, C. ^{[9
]}

Lotesoriere, C. ^{[10
]}

Vallarelli, S. ^{[10
]}

Lonardi, S. ^{[11
]}

Iacono, D. ^{[12
]}

Cremolini, C. ^{[13
,14
]}

Tortora, G. ^{[15
,16
]}

Tagliaferri, P. ^{[17
,18
]}

Pietrantonio, F. ^{[19
]}

Rosati, G. ^{[20
]}

Lucenti, A. ^{[21
]}

Scartozzi, M. ^{[22
]}

Brunetti, O. ^{[23
]}

Cinieri, S. ^{[24
]}

Zampino, M. G. ^{[1
]}

Zaniboni, A. ^{[25
]}

Berardi, R. ^{[26
]}

Paoletti, G. ^{[27
]}

Febbraro, A. ^{[28
]}

Martinelli, E. ^{[4
]}

Troiani, T. ^{[4
]}

Cioli, E. ^{[4
]}

Normanno, N. ^{[29
]}

Di Maio, M. ^{[30
]}

Parente, P. ^{[31
]}

Fazio, N. ^{[1
]}

Curigliano, G. ^{[2
,3
]}

De Vita, F. ^{[4
]}

Avallone, A. ^{[6
]}

Maiello, E. ^{[5
]}

Ciardiello, F. ^{[4
]}

Martini, G. ^{[4
]}

机构：

[1] European Inst Oncol, IRCCS, IEO, Div Gastrointestinal Med Oncol & Neuroendocrine Tu, Via Ripamonti 435, I-20141 Milan, Italy

[2] European Inst Oncol, IRCCS, Div New Drugs & Early Drug Dev Innovat Therapies, Milan, Italy

[3] Univ Milan, Dept Oncol & Hematooncol, Milan, Italy

[4] Univ Campania Luigi Vanvitelli, Dept Precis Med, Naples, Italy

[5] Fdn IRCCS Casa Sollievo Sofferenza, Med Genet Unit, San Giovanni Rotondo, Italy

[6] IRCCS Fdn G Pascale, Ist Nazl Tumori, IRCCS, Expt Clin Abdominal Oncol Unit, Naples, Italy

[7] Tricase City Hosp, Cardinale G Panico, Dept Oncol & Palliat Care, Tricase, Italy

[8] Azienda Osped ARNAS Garibaldi, Med Oncol Unit, Catania, Italy

[9] San Giuseppe Moscati Hosp, Med Oncol Unit, Statte, Italy

[10] IRCCS Bellis Res Hosp, Natl Inst Gastroenterol, Med Oncol Unit, Castellana Grotte, Italy

[11] Ist Oncol Veneto IOV IRCCS, Med Oncol 3, Padua, Italy

[12] Azienda Osped San Camillo Forlanini Roma, Med Oncol, Rome, Italy

[13] Univ Hosp Pisa, Unit Med Oncol 2, Pisa, Italy

[14] Univ Pisa, Dept Translat Res & New Technol Med & Surg, Pisa, Italy

[15] Policlin Univ A Gemelli IRCCS, Med Oncol, Rome, Italy

[16] Univ Cattolica Sacro Cuore, Dept Translat Med, Med Oncol, Rome, Italy

[17] Magna Graecia Univ Catanzaro, Dept Expt & Clin Med, Catanzaro, Italy

[18] AOU Renato Dulbecco, Med & Translat Oncol Unit, Catanzaro, Italy

[19] Fdn IRCCS Ist Nazl Tumori, Dept Med Oncol, Milan, Italy

[20] San Carlo Hosp, Med Oncol Unit, Potenza, Italy

[21] ASP 7 Ragusa, Med Oncol Unit, Ragusa, Italy

[22] Univ Cagliari, Azienda Osped Univ Cagliari, Dept Med Sci & Publ Hlth, Med Oncol Unit, Cagliari, Italy

[23] IRCCS Ist Tumori Giovanni Paolo II, Bari, Italy

[24] Osped Summa A Perrino, Med Oncol Unit, Brindisi, Italy

[25] Fdn Poliambulanza, Med Oncol Unit, Brescia, Italy

[26] Marche Polytech Univ, Dept Med Oncol, Ancona, Italy

[27] IRCCS Regina Elena Natl Canc Inst, Div Med Oncol 2, Rome, Italy

[28] Casa Cura Villa Maria UPMC Hillman Canc Ctr Mirabe, Med Oncol Unit, Avellino, Italy

[29] IRCCS Ist Romagnolo Studio Tumori IRST Dino Amador, Mendola, Italy

[30] Univ Turin, Molinette Hosp, Dept Radiol, I-10126 Turin, Italy

[31] Fdn IRCCS Casa Sollievo Sofferenza, Pathol Unit, San Giovanni Rotondo, Italy

来源：

ESMO OPEN | 2025年 / 10卷 / 04期

关键词：

colorectal cancer; liquid biopsy; cetuximab; comprehensive genomic profiling; CIRCULATING TUMOR DNA; RAS MUTATIONS; HETEROGENEITY; PROGRESSION; THERAPY;

D O I：

10.1016/j.esmoop.2025.104511

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Background: Limited evidence is currently available on the role of liquid biopsy (LBx) in predicting the efficacy of anti- epidermal growth factor receptor (EGFR) therapies in metastatic colorectal cancer (mCRC). Methods: The CAPRI-2 GOIM is a phase II trial investigating the use of LBx-comprehensive genomic profiling (CGP)guided, cetuximab-based treatment through three subsequent lines of therapy in patients with RAS/BRAF wild-type (WT) mCRC. LBx-CGP is carried out at baseline and at progressive disease to first- and second-line therapies. In case of RAS/BRAF WT circulating tumor DNA at progressive disease, EGFR therapeutic blockade is continued by combining cetuximab with a different chemotherapy backbone. The primary endpoint is overall response rate (ORR) by RECIST 1.1 criteria. Tumor molecular characteristics by LBx-CGP are correlated with treatment efficacy. Results: One hundred and ninety-two RAS/BRAF WT microsatellite stable mCRC patients treated with FOLFIRI plus cetuximab with baseline LBx-CGP and assessable for response were included in the analysis. One hundred and thirty-seven patients with WT tumors for potential anti-EGFR drug resistance genes (RAS/BRAF/EGFR/PIK3CA/ MAP2K1/MET/RET/ALK/ROS1/NTRK/NF1/FGFR, and HER2 amplification; 'negatively hyper-selected' cases) had 78.1% ORR compared with 54.5% ORR for patients with mutations [odds ratio 2.95, 95% confidence interval (CI) 1.44-6.10, P = 0.001]. 'Negatively hyper-selected' patients had median progression-free survival of 12.35 months (95% CI 10.58-15.4 months) compared with 8.68 months (95% CI 4.87-12.1 months) for patients with mutations (hazard ratio 0.64, 95% CI 0.44-0.92, P = 0.017). High cancer cell clonality of pathogenic variants (PVs) correlated with worse median progression-free survival (3.55 months, 95% CI 2.57 months to NE) compared with low cancer cell clonality of PV (9.63 months, 95% CI 7.16 months to NE, P 1/4 0.21). After first-line therapy failure, approximately one out of five patients had acquired PVs of potential anti-EGFR drug resistance genes, whereas RAS/BRAF WT circulating tumor DNA was maintained in most patients (78.5%). Conclusions: These results support the integration of LBx-CGP for implementing the efficacy and for optimizing the use of anti-EGFR therapies in RAS/BRAF WT mCRC.

引用

页数：11

共 29 条

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