Secondary resection is a chance of cure for a subgroup of metastatic colorectal cancer (mCRC) patients with unresectable liver-limited disease. Medical treatment has a dual goal: to induce tumour shrinkage and to prevent disease relapse. The aims of the present analysis were to assess the efficacy of FOLFOXIRI plus bevacizumab in this setting, and to investigate whether this regimen could revert the poor prognosis of high-risk patients defined by clinical and molecular factors. We performed a pooled analysis of patients with unresectable and liver-limited mCRC, treated with first-line FOLFOXIRI plus bevacizumab in three prospective clinical trials by Gruppo Oncologico del Nord Ovest. 205 (37.9%) patients with liver-limited disease were selected, out of 541 treated patients. Liver metastases were synchronous, ≥4 and bilobar in 90%, 61%, and 79% of cases, respectively. The largest diameter was >5 cm in 42% of cases, and ≥6 segments were involved in 25%. Seventy-four patients (36.1%) underwent R0 or R1 resection of metastases. R2 resections were performed in 17 cases (8.3%). Having <6 involved segments (p < 0.001) and achieving RECIST response (p = 0.019) were associated with higher chances of resection. R0/R1 resected patients had significantly longer median progression-free survival (PFS) (18.1 versus 10.7 months, HR: 0.48 [0.35-0.66], p < 0.001) and overall survival (OS) (44.3 versus 24.4 months, HR: 0.32 [0.22-0.48], p < 0.001) compared with other patients, both in the univariate and multivariate analyses (PFS p = 0.025; OS p < 0.001). The 5-year PFS and OS rate in R0 resected patients were 12% and 43%, respectively. Neither negative baseline characteristics nor high clinical risk scores or RAS/BRAF mutations were associated with poor post-resection outcomes. In conclusion, FOLFOXIRI plus bevacizumab demonstrates efficacy in the conversion setting with considerable long-term outcome results independent of clinical and molecular prognostic factors (NCT00719797, NCT01163396 and NCT02271464).

Efficacy of FOLFOXIRI plus bevacizumab in liver-limited metastatic colorectal cancer : a pooled analysis of clinical studies by Gruppo Oncologico del Nord Ovest / C. Cremolini, M. Casagrande, F. Loupakis, G. Aprile, F. Bergamo, G. Masi, R. Moretto R, F. Pietrantonio, F. Marmorino, G. Zucchelli, G. Tomasello, G. Tonini, G. Allegrini, C. Granetto, L. Ferrari, L. Urbani, U. Cillo, P. Pilati, E. Sensi, A. Pellegrinelli, M. Milione, G. Fontanini, A. Falcone. - In: EUROPEAN JOURNAL OF CANCER. - ISSN 0959-8049. - 73(2017), pp. 74-84. [10.1016/j.ejca.2016.10.028]

Efficacy of FOLFOXIRI plus bevacizumab in liver-limited metastatic colorectal cancer : a pooled analysis of clinical studies by Gruppo Oncologico del Nord Ovest

F. Pietrantonio;A. Pellegrinelli;
2017

Abstract

Secondary resection is a chance of cure for a subgroup of metastatic colorectal cancer (mCRC) patients with unresectable liver-limited disease. Medical treatment has a dual goal: to induce tumour shrinkage and to prevent disease relapse. The aims of the present analysis were to assess the efficacy of FOLFOXIRI plus bevacizumab in this setting, and to investigate whether this regimen could revert the poor prognosis of high-risk patients defined by clinical and molecular factors. We performed a pooled analysis of patients with unresectable and liver-limited mCRC, treated with first-line FOLFOXIRI plus bevacizumab in three prospective clinical trials by Gruppo Oncologico del Nord Ovest. 205 (37.9%) patients with liver-limited disease were selected, out of 541 treated patients. Liver metastases were synchronous, ≥4 and bilobar in 90%, 61%, and 79% of cases, respectively. The largest diameter was >5 cm in 42% of cases, and ≥6 segments were involved in 25%. Seventy-four patients (36.1%) underwent R0 or R1 resection of metastases. R2 resections were performed in 17 cases (8.3%). Having <6 involved segments (p < 0.001) and achieving RECIST response (p = 0.019) were associated with higher chances of resection. R0/R1 resected patients had significantly longer median progression-free survival (PFS) (18.1 versus 10.7 months, HR: 0.48 [0.35-0.66], p < 0.001) and overall survival (OS) (44.3 versus 24.4 months, HR: 0.32 [0.22-0.48], p < 0.001) compared with other patients, both in the univariate and multivariate analyses (PFS p = 0.025; OS p < 0.001). The 5-year PFS and OS rate in R0 resected patients were 12% and 43%, respectively. Neither negative baseline characteristics nor high clinical risk scores or RAS/BRAF mutations were associated with poor post-resection outcomes. In conclusion, FOLFOXIRI plus bevacizumab demonstrates efficacy in the conversion setting with considerable long-term outcome results independent of clinical and molecular prognostic factors (NCT00719797, NCT01163396 and NCT02271464).
Bevacizumab; FOLFOXIRI; Liver metastases; Metastatic colorectal cancer; Adult; Aged; Angiogenesis Inhibitors; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Camptothecin; Colorectal Neoplasms; Disease-Free Survival; Female; Fluorouracil; Humans; Kaplan-Meier Estimate; Leucovorin; Liver Neoplasms; Male; Middle Aged; Multivariate Analysis; Organoplatinum Compounds; Prospective Studies; Young Adult; Oncology; Cancer Research
Settore MED/06 - Oncologia Medica
Article (author)
File in questo prodotto:
File Dimensione Formato  
N°77 Efficacy of FOLFOXIRI plus bevacizumab in liver-limited.pdf

accesso riservato

Tipologia: Publisher's version/PDF
Dimensione 1.09 MB
Formato Adobe PDF
1.09 MB Adobe PDF   Visualizza/Apri   Richiedi una copia
Pubblicazioni consigliate

Caricamento pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/563970
Citazioni
  • ???jsp.display-item.citation.pmc??? 11
  • Scopus 37
  • ???jsp.display-item.citation.isi??? 35
social impact