Randomized phase II trial of FOLFIRI-panitumumab compared with FOLFIRI alone in patients with RAS wild-type circulating tumor DNA metastatic colorectal cancer beyond progression to first-line FOLFOX-panitumumab: the BEYOND study (GEMCAD 17-01)
Por:
Aparicio, J, Manrique, ACV, Capdevila, J, Boza, FM, Galvan, P, Richart, P, Oliveres, H, Paez, D, Hernando, J, Serrano, S, Vera, R, Hernandez-Yague, X, Gallego, RA, Riesco-Martinez, MC, de Albeniz, XG, Maurel, J
Publicada:
1 nov 2022
Ahead of Print:
1 jun 2022
Resumen:
Purpose Panitumumab plus FOLFOX (P-FOLFOX) is standard first-line treatment for RAS wild-type (WT) metastatic colorectal cancer. The value of panitumumab rechallenge is currently unknown. We assessed addition of panitumumab to FOLFIRI (P-FOLFIRI) beyond progression to P-FOLFOX in patients with no RAS mutations in liquid biopsy (LB). Methods In this randomized phase II trial, patients were assigned (3:2 ratio) to second-line P-FOLFIRI (arm A) or FOLFIRI alone (arm B). LB for circulating tumor DNA analysis was collected at study entry and at disease progression. Primary endpoint was 6-month progression-free survival. Two-stage Simon design required 85 patients to be included (EudraCT 2017-004519-38). Results Between February 2019 and November 2020, 49 patients were screened (16 RAS mutations in LB detected) and 31 included (18 assigned to arm A and 13 to arm B). The study was prematurely closed due to inadequate recruitment. Serious adverse events were more frequent in arm A (44% vs. 23%). Overall response rate was 33% (arm A) vs. 7.7% (arm B). Six-month progression-free survival rate was 66.7% (arm A) and 38.5% (arm B). Median progression-free survival was 11.0 months (arm A) and 4.0 months (arm B) (hazard ratio, 0.58). At disease progression, RAS or BRAF mutations in LB were found in 4/11 patients (36%) in arm A and 2/10 (20%) in arm B. Conclusions The BEYOND study suggests a meaningful benefit of P-FOLFIRI beyond progression to P-FOLFOX in metastatic colorectal cancer patients with WT RAS status selected by LB. This strategy deserves further investigation.
Filiaciones:
Aparicio, J:
Hosp Univ & Politecn La Fe, Med Oncol Dept, Avda Abril Martorell 106, Valencia 46026, Spain
Manrique, ACV:
Hosp Santa Creu & Sant Pau, Med Oncol Dept, Barcelona, Spain
Capdevila, J:
Vall dHebron Univ Hosp, Vall Hebron Inst Oncol VHIO, Med Oncol Dept, Barcelona, Spain
IOB Teknon, Barcelona, Spain
Boza, FM:
Hosp Univ St Joan Reus, Med Oncol Dept, Reus, Spain
Galvan, P:
Hosp Clin Barcelona, Med Oncol Dept, Translat Genom & Targeted Therapies Solid Tumors, C Villaroel 170, Barcelona 08036, Spain
Richart, P:
Hosp Univ & Politecn La Fe, Med Oncol Dept, Avda Abril Martorell 106, Valencia 46026, Spain
Oliveres, H:
Hosp Clin Barcelona, Med Oncol Dept, Translat Genom & Targeted Therapies Solid Tumors, C Villaroel 170, Barcelona 08036, Spain
Paez, D:
Hosp Santa Creu & Sant Pau, Med Oncol Dept, Barcelona, Spain
Hernando, J:
Vall dHebron Univ Hosp, Vall Hebron Inst Oncol VHIO, Med Oncol Dept, Barcelona, Spain
Serrano, S:
Hosp Univ St Joan Reus, Med Oncol Dept, Reus, Spain
Vera, R:
Complejo Hosp Navarra, Med Oncol Dept, Pamplona, Spain
Hernandez-Yague, X:
ICO, Med Oncol Dept, Girona, Spain
Gallego, RA:
Hosp Madrid Norte San Chinarro, Med Oncol Dept, Ctr Integral Oncol Clara Campal, Madrid, Spain
Riesco-Martinez, MC:
Hosp Univ 12 Octubre, Med Oncol Dept, Madrid, Spain
de Albeniz, XG:
RTI Hlth Solut, Barcelona, Spain
Maurel, J:
Hosp Clin Barcelona, Med Oncol Dept, Translat Genom & Targeted Therapies Solid Tumors, C Villaroel 170, Barcelona 08036, Spain
hybrid, Hybrid Gold
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