{Reference Type}: Clinical Trial, Phase II
{Title}: 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).
{Author}: Aparicio J;Virgili Manrique AC;Capdevila J;Muñoz Boza F;Galván P;Richart P;Oliveres H;Páez D;Hernando J;Serrano S;Vera R;Hernandez-Yagüe X;Gallego RÁ;Riesco-Martinez MC;García de Albeniz X;Maurel J;
{Journal}: Clin Transl Oncol
{Volume}: 24
{Issue}: 11
{Year}: Nov 2022
{Factor}: 3.34
{DOI}: 10.1007/s12094-022-02868-x
{Abstract}: <B>OBJECTIVE: </B>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).<BR><B>METHODS: </B>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).<BR><B>RESULTS: </B>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.<BR><B>CONCLUSIONS: </B>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.