Background: First-line FOLFOXIRI demonstrated superior activity and efficacy compared to FOLFIRI. Moreover, the outcome is improved by the addition of bev to first-line doublets. A phase II study of FOLFOXIRI/bev showed promising activity and manageable toxicities. The present trial compared FOLFOXIRI/bev to FOLFIRI/bev as first-line treatment in unresectable mCRC. Methods: Eligibility criteria included: measurable and unresectable mCRC, age 18-75 years, no prior chemotherapy for advanced disease. Patients (pts) were randomized to either FOLFIRI/bev (bev 5 mg/kg, irinotecan 180 mg/sqm, l-LV 200 mg/sqm, 5FU bolus 400 mg/sqm, 5FU infusion 2400 mg/sqm over 48h q2w, arm A) or FOLFOXIRI/bev (bev 5 mg/kg, irinotecan 165 mg/sqm, oxaliplatin 85 mg/sqm, l-LV 200 mg/sqm, 5FU infusion 3200 mg/sqm over 48h q2w, arm B). Treatment was planned for a maximum of 12 cycles followed by maintenance with bev and 5FU until progression. Primary endpoint was progression-free survival (PFS). Results: Between July 2008 and May 2011, 508 pts were randomized among 35 italian centers. Pts characteristics were (arm A/arm B): median age 60/61 yrs, ECOG PS 1-2 11%/10%, synchronous metastases 81%/79% multiple sites of disease 74%/70%. At a median follow-up of 20.9 months 391 pts have progressed. The study met its primary endpoint: FOLFOXIRI/bev significantly increased PFS (median 9.5 vs 11.9 months, HR 0.72 [95%CI:0.59-0.87], p=0.001). Response rate was also significantly increased (53% vs 64%, p=0.015). Main per patient toxicities were (arm A/arm B): grade 3-4 diarrhea 10%/18%, grade 3-4 vomiting 3%/4%, grade 3-4 stomatitis 4%/8%, grade 3-4 peripheral neurotoxicity 0%/5%, grade 3-4 neutropenia 20%/49%, febrile neutropenia 6%/8%, hypertension 2%/4%, thromboembolic events 7%/7%, bleeding 1%/1%. Deaths within 60 days were 3% and 4%. Conclusions: FOLFOXIRI/bev significantly increases PFS and response rate compared to FOLFIRI/bev. Chemotherapy- and bev-related toxicities occur with the expected incidence. Clinical trial information: NCT00719797.
FOLFOXIRI plus bevacizumab (bev) versus FOLFIRI plus bev as first-line treatment of metastatic coloectal cancer (MCRC): results of the phase III tandomized TRIBE trial / Luopakis, F; Cremolini, C; Masi, G; Lonardi, S; Zagonel, V; Trenta, P; Tomasello, G; Ronzoni, M; Ciuffreda, L; Zaniboni, A; Tonini, G; Buonadonna, A; Valsuani, C; Chiara, S; Carlomagno, Chiara; Boni, C; Marcucci, L; Boni, L; Falcone, A.. - In: JOURNAL OF CLINICAL ONCOLOGY. - ISSN 0732-183X. - STAMPA. - 30:(2013).
FOLFOXIRI plus bevacizumab (bev) versus FOLFIRI plus bev as first-line treatment of metastatic coloectal cancer (MCRC): results of the phase III tandomized TRIBE trial
CARLOMAGNO, Chiara;
2013
Abstract
Background: First-line FOLFOXIRI demonstrated superior activity and efficacy compared to FOLFIRI. Moreover, the outcome is improved by the addition of bev to first-line doublets. A phase II study of FOLFOXIRI/bev showed promising activity and manageable toxicities. The present trial compared FOLFOXIRI/bev to FOLFIRI/bev as first-line treatment in unresectable mCRC. Methods: Eligibility criteria included: measurable and unresectable mCRC, age 18-75 years, no prior chemotherapy for advanced disease. Patients (pts) were randomized to either FOLFIRI/bev (bev 5 mg/kg, irinotecan 180 mg/sqm, l-LV 200 mg/sqm, 5FU bolus 400 mg/sqm, 5FU infusion 2400 mg/sqm over 48h q2w, arm A) or FOLFOXIRI/bev (bev 5 mg/kg, irinotecan 165 mg/sqm, oxaliplatin 85 mg/sqm, l-LV 200 mg/sqm, 5FU infusion 3200 mg/sqm over 48h q2w, arm B). Treatment was planned for a maximum of 12 cycles followed by maintenance with bev and 5FU until progression. Primary endpoint was progression-free survival (PFS). Results: Between July 2008 and May 2011, 508 pts were randomized among 35 italian centers. Pts characteristics were (arm A/arm B): median age 60/61 yrs, ECOG PS 1-2 11%/10%, synchronous metastases 81%/79% multiple sites of disease 74%/70%. At a median follow-up of 20.9 months 391 pts have progressed. The study met its primary endpoint: FOLFOXIRI/bev significantly increased PFS (median 9.5 vs 11.9 months, HR 0.72 [95%CI:0.59-0.87], p=0.001). Response rate was also significantly increased (53% vs 64%, p=0.015). Main per patient toxicities were (arm A/arm B): grade 3-4 diarrhea 10%/18%, grade 3-4 vomiting 3%/4%, grade 3-4 stomatitis 4%/8%, grade 3-4 peripheral neurotoxicity 0%/5%, grade 3-4 neutropenia 20%/49%, febrile neutropenia 6%/8%, hypertension 2%/4%, thromboembolic events 7%/7%, bleeding 1%/1%. Deaths within 60 days were 3% and 4%. Conclusions: FOLFOXIRI/bev significantly increases PFS and response rate compared to FOLFIRI/bev. Chemotherapy- and bev-related toxicities occur with the expected incidence. Clinical trial information: NCT00719797.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
