Randomized phase III study comparing FOLFOX + bevacizumab versus folfoxiri + bevacizumab (BEV) as 1st line treatment in patients with metastatic colorectal cancer (mCRC) with ≥3 baseline circulating tumor cells (bCTCs).

person Javier Sastre Hospital Clínico San Carlos, Instituto de Investigación Hospital Clinico San Carlos (IdISSC), Madrid/Spain, CIBERONC, Madrid, Spain info_outline Javier Sastre, Jose María Vieitez, Maria Auxilidora Gomez-España, Silvia Gil Calle, Antonieta Salud Salvia, Begoña Graña Suárez, Pilar Garcia-Alfonso, Eva Martinez de Castro, Guillermo Alfonso Quintero Aldana, Juan José Reina-Zoilo, Encarnación González Flores, Mercedes Salgado Fernández, Carmen Guillen, Rocio Garcia-Carbonero, Maria Jose Safont, Adelaida La Casta Munoa, Beatriz García de Paredes, Rafael Lopez, Enrique Aranda, Eduardo Díaz-Rubio

Authors person Javier Sastre Hospital Clínico San Carlos, Instituto de Investigación Hospital Clinico San Carlos (IdISSC), Madrid/Spain, CIBERONC, Madrid, Spain info_outline Javier Sastre, Jose María Vieitez, Maria Auxilidora Gomez-España, Silvia Gil Calle, Antonieta Salud Salvia, Begoña Graña Suárez, Pilar Garcia-Alfonso, Eva Martinez de Castro, Guillermo Alfonso Quintero Aldana, Juan José Reina-Zoilo, Encarnación González Flores, Mercedes Salgado Fernández, Carmen Guillen, Rocio Garcia-Carbonero, Maria Jose Safont, Adelaida La Casta Munoa, Beatriz García de Paredes, Rafael Lopez, Enrique Aranda, Eduardo Díaz-Rubio Organizations Hospital Clínico San Carlos, Instituto de Investigación Hospital Clinico San Carlos (IdISSC), Madrid/Spain, CIBERONC, Madrid, Spain, Hospital Universitario Central de Asturias, Oviedo, Spain, IMIBIC, Reina Sofía Hospital, University of Córdoba, CIBERONC, Instituto de Salud Carlos III, Córdoba, Spain, H. Universitario y Regional y Virgen de la Victoria, Malaga, Spain, Hospital de Lleida Arnau de Vilanova, Lérida, Spain, University Hospital A Coruña, Sergas, Spain, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain, Hospital Universitario Marqués de Valdecilla, Santander, Spain, Hospital Universitario Lucus Augusti, Lugo, Spain, Complejo Universitario Virgen de la Macarena, Sevilla, Spain, H. Virgen de las Nieves, Granada, Spain, Complexo Hospitalario Universitario de Ourense, Ourense, Spain, Hospital Universitario Ramón y Cajal, Madrid, Spain, Hospital Virgen del Rocío, Sevilla, Spain, Hospital General Universitario de Valencia, Valencia, Spain, Hospital Universitario Donostia, San Sebastian, Spain, Hospital Clínico San Carlos, Instituto de Investigación Hospital Clinico San Carlos (IdISSC), CIBERONC, Madrid, Spain, University Clinical Hospital and Health Research Institute (IDIS), CIBERONC, Santiago de Compostela University School of Medicine, Santiago De Compostela, Spain, IMIBIC, Reina Sofía Hospital, University of Córdoba, CIBERONC, Instituto de Salud Carlos III/ Spain, Córdoba, Spain Abstract Disclosures Research Funding Pharmaceutical/Biotech Company Background: FOLFOXIRI+BEV has demonstrated a survival benefit compared with FOLFIRI plus BEV (TRIBE Lancet Oncol 2015) in first-line mCRC. Nevertheless, due to its safety profile, this schedule is not recommended for all pts. In addition, we have showed that the detection of ≥3 bCTCs is a poor prognostic factor for survival (MACRO The Oncologist 2012). The VISNU-1 trial compares FOLFOX + BEV vs FOLFOXIRI + BEV in pts with mCRC and ≥3 bCTCs. Progression-free survival (PFS) is the primary endpoint. Secondary endpoints included overall response rate (ORR) and overall survival (OS). Methods: This is an open, multicentric, randomized phase III trial. Patients with mCRC younger than 70 years, ECOG 0-1 were randomized to FOLFOX+BEV (arm A) or FOLFOXIRI+BEV (arm B), stratified per KRAS mutation (mutated vs WT) and number of involved organs (1 vs >1). Results: 349 pts were included in the ITT population; 177 in group A and 172 in group B. Characteristics of the pts, molecular profiling and safety analysis have been previously presented at ASCO 2018 and showed that this schedule had an acceptable toxicity profile. Efficacy analysis in the ITT population is shown in the table. Conclusions: In this population with very bad prognosis, our study met its primary endpoint. Pts who received FOLFOXIRI + Bev benefit for a statistically significative PFS and ORR. OS showed a trend of benefit in the experimental arm. According to these results, FOLFOXIRI-Bev could be considered an adequate treatment option for pts with mCRC and ≥3 bCTCs. Clinical trial information: 2012-000846-37. Variable FOLFOX + Bev n=177 FOLFOXIRI + Bev n= 172 p value PFS (median in m) 9.3 12.4 P=0.0004 ORR (%) 52.0 59.0 0.1685 OS (median in m) 17.6 21.7 0.862