Randomized phase II study on the influence of BRAF and PIK3CA mutations on the efficacy of FOLFIRI plus bevacizumab (Bev) or cetuximab (Cet), as first line therapy of patients (pts) with RAS wild-type metastatic colorectal carcinoma (mCRC) and <3 baseline circulating tumor cells (bCTCs).

person Enrique Aranda IMIBIC, Reina Sofía Hospital, University of Córdoba, CIBERONC, Instituto de Salud Carlos III/ Spain, Córdoba, Spain info_outline Enrique Aranda, Pilar Garcia-Alfonso, Jose María Vieitez, Maria Jose Ortiz, Carlos López-López, Juan José Reina-Zoilo, Antonieta Salud Salvia, Guillermo Alfonso Quintero Aldana, Luis Robles, Maria Jose Safont, Adelaida La Casta Munoa, Inmaculada Alés, Eduardo Polo Marques, Javier Gallego Plazas, Beatriz García de Paredes, Rafael Lopez, Guillot Mónica, Manuel Valladares-Ayerbes, Javier Sastre, Eduardo Díaz-Rubio

Authors person Enrique Aranda IMIBIC, Reina Sofía Hospital, University of Córdoba, CIBERONC, Instituto de Salud Carlos III/ Spain, Córdoba, Spain info_outline Enrique Aranda, Pilar Garcia-Alfonso, Jose María Vieitez, Maria Jose Ortiz, Carlos López-López, Juan José Reina-Zoilo, Antonieta Salud Salvia, Guillermo Alfonso Quintero Aldana, Luis Robles, Maria Jose Safont, Adelaida La Casta Munoa, Inmaculada Alés, Eduardo Polo Marques, Javier Gallego Plazas, Beatriz García de Paredes, Rafael Lopez, Guillot Mónica, Manuel Valladares-Ayerbes, Javier Sastre, Eduardo Díaz-Rubio Organizations IMIBIC, Reina Sofía Hospital, University of Córdoba, CIBERONC, Instituto de Salud Carlos III/ Spain, Córdoba, Spain, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain, Hospital Universitario Central de Asturias, Oviedo, Spain, IMIBIC, Reina Sofía Hospital, Univeristy of Córdoba, CIBERONC, Instituto de Salud Carlos III, Córdoba, Spain, Marqués de Valdecilla University Hospital, Santander, Spain, Complejo Universitario Virgen de la Macarena, Sevilla, Spain, Hospital de Lleida Arnau de Vilanova, Lérida, Spain, Hospital Universitario Lucus Augusti, Lugo, Spain, Hospital 12 de Octubre, Madrid, Spain, Hospital General Universitario de Valencia, Valencia, Spain, Hospital Universitario Donostia, San Sebastian, Spain, Hospital Universitario Regional Virgen de la Victoria, Málaga, Spain, Hospital Miguel Servet, Zaragoza, Spain, Hospital General Universitario de Elche, Elche, 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, Hospital Son Espases, Palma De Mallorca, Spain, Complejo Hospitalario Universitario A Coruña, Instituto de Investigación Biomédica (INIBIC), A Coruña, Spain, Hospital Clínico San Carlos, Instituto de Investigación Hospital Clinico San Carlos (IdISSC), Madrid/Spain, CIBERONC, Madrid, Spain Abstract Disclosures Research Funding Pharmaceutical/Biotech Company Background: The outcome for mCRC has changed since the introduction of new chemotherapy schedules and targeted therapies, however new predictive biomarkers are needed. bCTCs and BRAF / PIK3CA mutations have been studied as a potential predictive biomarkers. The primary endpoint was progression-free survival (PFS) in pts WT KRAS and <3 bCTCs, according to BRAF / PIK3CA status. Methods: This is an open, multicentric, randomized phase II trial and included wildtype KRAS mCRC pts (RAS after approval of protocol amendment), younger than ≤70 with <3 bCTCs, ECOG 0-1 and available tissue for molecular analyses. Pts were stratified per number of metastatic organs involved (1 vs >1) and mutation status of BRAF and/or PIK3CA (WT vs MUT) and randomized to group A (FOLFIRI+Bev) or group B (FOLFIRI+Cet). Results: 240 pts (196 WT and 44 MUT: 6 BRAF , 12 PIK3CA and 6 BRAF + PIK3CA ) were included. General characteristics per mutation status (WT vs MUT): Mean age (59 vs 61 years), gender (Male/Female 68/32 vs 70/30%), ECOG 0/1 (57/43 vs 66/34%), primary tumor unresected (48 vs 64%), RAS MUT in 12 pts (11 and 1 pts, respectively), previous chemotherapy (12 vs 9%). Overall response rate (ORR) was 52 and 41% in the WT and MUT groups, respectively. PFS and overall survival (OS) are presented in the table. Conclusions: In the low risk mCRC pts according to bCTCs, BRAF and/or PIK3CA MUT have a negative impact in OS and a trend to worse PFS in the ITT population. The impact of treatment is under evaluation and will be provided during the meeting. Clinical trial information: 2012-000840-90. ITT population N=240 FOLFIRI + Bev N=126 FOLFIRI + Cet N=114 WT N=196 MUT N=44 HR (IC95%) p value WT N=102 MUT N=24 All HR (IC95%) p value WT N=94 MUT N=20 All HR (IC95%) p value PFS m 12.7 9.1 1.136 (0.739-1.745) p =0.562 12.9 9.3 12.5 0.992 (0.554-1.776) p =0.978 12.5 8.5 11,5 1.452 (0.765-2.755) p= 0.253 OS m 34,7 20,7 1.878 (1.269-2.779) p =0.0016 36.0 18.6 32,9 2.022 (1.194-3.425) p =0.008 34.1 23.7 33.3 1.714 (0.947-3.102) p =0.078