Primary tumor sidedness and benefit from FOLFOXIRI plus bevacizumab as initial therapy for metastatic colorectal cancer. Retrospective analysis of the TRIBE trial by GONO

被引：92

作者：

Cremolini, C. ^{[1
,2
]}

Antoniotti, C. ^{[1
,2
]}

Lonardi, S. ^{[3
]}

Bergamo, F. ^{[3
]}

Cortesi, E. ^{[4
]}

Tomasello, G. ^{[5
]}

Moretto, R. ^{[1
,2
]}

Ronzoni, M. ^{[6
]}

Racca, P. ^{[7
]}

Loupakis, F. ^{[1
,3
]}

Zaniboni, A. ^{[8
]}

Tonini, G. ^{[9
]}

Buonadonna, A. ^{[10
]}

Marmorino, F. ^{[1
,2
]}

Allegrini, G. ^{[11
]}

Granetto, C. ^{[12
]}

Masi, G. ^{[1
,2
]}

Zagonel, V. ^{[3
]}

Sensi, E. ^{[13
]}

Fontanini, G. ^{[14
]}

Boni, L. ^{[15
]}

Falcone, A. ^{[1
,2
]}

机构：

[1] Azienda Osped Univ Pisana, Unit Med Oncol 2, Pisa, Italy

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

[3] Ist Oncol Veneto IRCCS, Unit Med Oncol 1, Dept Clin & Expt Oncol, Padua, Italy

[4] Univ Roma La Sapienza, Dept Med Oncol, Rome, Italy

[5] ASST Osped Cremona, Oncol Dept, Cremona, Italy

[6] San Raffaele Hosp IRCSS, Dept Oncol, Milan, Italy

[7] AOU Citta Salute Sci Torino, Dept Med Oncol, SSD ColoRectal Unit, Turin, Italy

[8] Poliambulanza Fdn, Dept Med Oncol, Brescia, Italy

[9] Univ Campus Biomed, Dept Med Oncol, Rome, Italy

[10] Ctr Riferimento Oncol, Div Oncol, Aviano, Italy

[11] Azienda Toscana Nord Ovest, Unit Med Oncol, Hosp Felice Lotti, Pontedera, Italy

[12] Azienda Sanit Osped Santa Croce & Carle, Unit Med Oncol, Cuneo, Italy

[13] Azienda Osped Univ Pisana, Unit Pathol 3, Pisa, Italy

[14] Univ Pisa, Dept Surg Med Mol Pathol & Crit Area, Pisa, Italy

[15] Univ Hosp Careggi, Ist Toscano Tumori, Clin Trials Coordinating Ctr, Florence, Italy

来源：

ANNALS OF ONCOLOGY | 2018年 / 29卷 / 07期

关键词：

metastatic colorectal cancer; primary sidedness; FOLFOXIRI plus bevacizumab; RAS and BRAF mutational status; 1ST-LINE TREATMENT; ANTIBODIES; LOCATION; FOLFIRI; DISTAL; RAS;

D O I：

10.1093/annonc/mdy140

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Background: Right-sided metastatic colorectal cancer (mCRC) patients have poor prognosis and achieve limited benefit from first-line doublets plus a targeted agent. In this unplanned analysis of the TRIBE study, we investigated the prognostic and predictive impact of primary tumor sidedness in mCRC patients and the differential impact of the intensification of the chemotherapy in subgroups defined according to both primary tumor sidedness and RAS and BRAF mutational status. Patients and methods: Patients were randomized to receive upfront 5-fluoruracil, leucovorin, and irinotecan (FOLFIRI) plus bevacizumab or 5-fluoruracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI) plus bevacizumab. Tumors were defined as right-or left-sided if they originated from the caecum to the transverse colon or within the splenic flexure and beyond, respectively. Patients with available information about both primary sidedness and RAS and BRAF status were included in the present analysis. Progression-free survival (PFS), overall survival (OS) and RECIST response rate were assessed according to tumor location and RAS and BRAF mutational status. Results: Information about primary sidedness and RAS and BRAF status was available for 358 (70.5%) out of 508 randomized patients. Patients with right-sided tumors (N = 173) presented shorter OS [23.7 versus 31.0 months, HR = 1.42 (95% CI 1.09-1.84), P = 0.010] and a trend toward shorter PFS [10.2 versus 11.5 months, HR = 1.24 (95% CI: 0.98-1.56), P = 0.083] than those with left-sided tumors (N = 185), but these associations were no longer evident when adjusting for RAS and BRAF status. Patients with right-sided tumors achieved more relative benefit from the intensification of the chemotherapy backbone in terms of both PFS (HR = 0.59 versus 0.89, P for interaction = 0.099) and OS (HR = 0.56 versus 0.99, P for interaction = 0.030) and this advantage was independent of their RAS and BRAF status. Conclusions: FOLFOXIRI plus bevacizumab may be regarded as a preferred first-line treatment option for clinically selected patients with right-sided metastatic colorectal cancer irrespective of their RAS and BRAF mutational status. Trial registration: clinicaltrials.gov identifier NCT00719797.

引用

页码：1528 / 1534

页数：7

共 15 条

[1] Prognostic and predictive value of primary tumour side in patients with RAS wild-type metastatic colorectal cancer treated with chemotherapy and EGFR directed antibodies in six randomized trials [J].