0000000000239912

AUTHOR

Reija Koukakis

Impact of Baseline Covariates and Prior Therapy on the Efficacy of Second-Line Panitumumab (Pmab) + Folfiri Vs Folfiri Treatment

ABSTRACT Aim: Expanding RAS analyses beyond KRAS exon 2 is important in selecting patients (pts) for pmab treatment. Here we present prespecified subgroup analyses from a phase 3 randomised second-line pmab + FOLFIRI vs FOLFIRI study in metastatic colorectal cancer (mCRC) pts. Methods: Progression-free (PFS) and overall survival (OS) were co-primary endpoints. KRAS exon 2 wild-type (WT) samples were tested for mutations in KRAS exons 3/4, NRAS exons 2/3/4 and BRAF exon 15 via bidirectional Sanger sequencing and WAVE-based SURVEYOR®. PFS and OS subgroup analyses were performed by randomisation stratification factors (ECOG performance status [PS], prior bevacizumab [bev]/prior oxaliplatin [ox…

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Tumour Shrinkage and Response Outcomes During Second-Line Panitumumab (Pmab) + Folfiri Vs Folfiri Treatment

ABSTRACT Aim: Tumour shrinkage/response are important outcomes for patients (pts) with metastatic colorectal cancer (mCRC) as they may delay progression and ultimately improve survival. Here we report tumour response data for pts with RAS WT mCRC treated with FOLFIRI ± pmab. Methods: 181 was a phase 3 randomised study of second-line pmab + FOLFIRI vs FOLFIRI alone in pts with previously treated mCRC. KRAS exon 2 wild-type (WT) samples from this study were tested for mutations in KRAS exons 3/4 and NRAS exons 2/3/4 via bidirectional Sanger sequencing and WAVE-based SURVEYOR® to identify pts with RAS WT tumours (no mutations in KRAS/NRAS exons 2, 3 or 4). Objective response rates (ORRs) and m…

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Analysis of KRAS/NRAS mutations in a phase III study of panitumumab with FOLFIRI compared with FOLFIRI alone as second-line treatment for metastatic colorectal cancer

Abstract Purpose: We evaluated the influence of RAS mutation status on the treatment effect of panitumumab in a prospective–retrospective analysis of a randomized, multicenter phase III study of panitumumab plus fluorouracil, leucovorin, and irinotecan (FOLFIRI) versus FOLFIRI alone as second-line therapy in patients with metastatic colorectal cancer (mCRC; ClinicalTrials.gov, NCT0039183). Experimental Design: Outcomes were from the study's primary analysis. RAS mutations beyond KRAS exon 2 (KRAS exons 3, 4; NRAS exons 2, 3, 4; BRAF exon 15) were detected by bidirectional Sanger sequencing in wild-type KRAS exon 2 tumor specimens. Progression-free survival (PFS) and overall survival (OS) we…

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