This trial evaluated activity and safety of mFOLFOXIRI + panitumumab vs FOLFOXIRI in ECOG 0-1, primarily non-resectable mCRC patients.
Prospective 2:1 randomized, multi-center, phase II trial comparing mFOLFOXIRI (Ox 85, Iri 150, 5-FU 3000, LV 200) + Panitumumab 6 mg/KG (arm A) with FOLFOXIRI (Ox 85, Iri 165, 5-FU 3200 cont. 48h, LV 200; arm B). Cohort 1: irresectable mCRC; cohort 2: chance of secondary resection of metastatic lesions. Primary endpoint: ORR, secondary endpoints: secondary resection rate, DCR, PFS, OS, toxicity, QL (QLQ-C30). Financially supported by an unrestricted grant from Amgen.
A total of 96 patients were randomized (63 arm A, 33 arm B). After an observation time of 29 months in both arms, final ORR results are displayed in the table. PFS in arm A reached 9.7 mo, in arm B 10.1 mo (HR 0.92, p=n.s.). PFS cohort II was 13.0 vs 9.0 mo in arm A and B, respectively (HR0.457, p = 0.068). PFS in BRAF mutated was comparable between arm A and B (6.5 vs 6.1 mo, HR 1.368, n.s.). Secondary resections were achieved in 33.3% (arm A) and 12.1% (arm B), R0 in 61.9% vs. 75.0%, respectively. In cohort 1, resections were achieved in 14% vs 0%, in cohort 2 in 75% vs 36.4%. RFS after resection of metastases was 7.9 vs 4.0 months in arm A and B, respectively (HR 0.623, p=n.s.). Treatment related adverse advents grade 3-5 occured in 81.3% and 66.7% in arms A and B, respectively (p = 0.1336). Non.haematological AEs grade 3-5 were more frequent in arm A (71.9%) than in arm B (39.4%), p = 0.0039. Nevertheless, no differences in global health status, functional scales, and symptom scales were reported.Table: 453PD
|mFOLFOXIRI +Pmab||FOLFOXIRI||p-value||Odds Ratio||95%-CI|
|ITT, n = 96||87.3||60.6||0.0041||4.469||1.614-12.376|
|Cohort II, n = 31||100.0||63.3||0.0105||24.6||1.1778-513.8|
|Left, n = 78||90.6||68.0||0.0210||4.518||1.298-15.718|
|Right, n = 18||70.0||37.5||0.3416||3.889||0.543-27.886|
|RAS/BRAF wt, n = 60||86.0||64.7||0.0806||3.364||0.902-12.549|
|BRAF mut, n = 16||85.7||22.2||0.0406||21.000||1.504-293.25|
mFOLFOXIRI + Panitumumab results in significantly higher ORR compared to FOLFOXIRI. Strong effectivity was observed also in right sided and BRAF mutated CRC. High secondary resection rates could be achieved. Although toxicity (treatment related SAEs) was increased, QL reporting was similar in both arms. OS is still immature, but will be presented first time at the meeting.
Clinical trial identification
Legal entity responsible for the study
AIO Studien GmbH.
M. Geissler: Honararium, advisory boards: Amgen, Sanofi, Merck, Lilly. All other authors have declared no conflicts of interest.