Abstract
3561 Background: Activating RAS mutation is a negative predictor of anti-EGFR therapy. In the final analysis of 20100007, the first phase 3 study to prospectively evaluate efficacy and safety of WT RAS ( KRAS and NRAS exons 2, 3, 4 ) mCRC, pmab + BSC continued to show improved survival (OS and PFS) and ORR. Recent data suggest that tumor burden reduction and ETS may contribute to improved OS. Previous studies have shown that pmab plus chemotherapy results in ETS, which correlates with OS benefit (Douillard et al, EJC, 2015; Rivera et al, JCO, 2015; Mansmann et al, JCO 2013). Here we report analyses of ETS and DpR and the effect on OS in patients (pts) with WT RAS mCRC treated with pmab monotherapy in the ‘0007 trial. Methods: Anti-EGFR naïve pts with WT KRAS exon 2 mCRC were randomized 1:1 to pmab + BSC or BSC. Pt tumors were further evaluated for RAS status, and DpR (percent tumor shrinkage at nadir or progression) and ETS (≥/< 0% or ≥/< 20% by week 8) were analyzed in WT RAS pts. OS and PFS were compared for each ETS group. Results: Of 377 pts with WT KRAS exon 2 mCRC, 270 were WT RAS (142 pmab + BSC, 128 BSC alone). In the pmab + BSC arm, 69.5% and 38.2% of pts had ≥0% and ≥20% ETS, respectively, and median (Q1, Q3) DpR was 16.9% (0%, 37.5%). OS was improved in pts with higher ETS (≥0% or ≥20%) compared with lower ETS (<0% or <20%; Table). Conclusions: In this post-hoc analysis, pmab monotherapy provided any ETS benefit (≥0%) in 69.5% of WT RAS mCRC pts, and ETS was associated with improved PFS and OS. Pmab should be considered both in combination and as monotherapy for its significant impact on OS and also for its ability for substantial ETS in pts with WT RAS mCRC. Validation is necessary to investigate the value and cutoff of ETS in a prospective study. Clinical trial information: NCT01412957. [Table: see text]
Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
