First-line treatment with modified FOLFOX6 (mFOLFOX6) + panitumumab (pmab) or bevacizumab (bev) in wild-type (WT) <i>RAS</i> metastatic colorectal carcinoma (mCRC): Tumor response outcomes beyond RECIST.

Abstract

660 Background: In the PEAK study, pmab + FOLFOX6 was associated with longer OS than bev + FOLFOX6 in first-line RAS WT mCRC. RECIST overall response rates (ORR) were similar between treatment arms. Here, we report exploratory analyses of tumour assessments beyond RECIST. Methods: PEAK was a randomised phase II study of first-line pmab + mFOLFOX6 vs bev + mFOLFOX6 in previously untreated mCRC. ORRs (investigator assessed), median duration of response (DoR; from first confirmed response to disease progression or death [secondary endpoint]) and depth of response (DpR; defined as the percentage of tumour shrinkage at nadir or progression) in RAS WT pts were calculated by treatment. Early tumour shrinkage (ETS) was defined as the proportion of patients with ≥30% tumour shrinkage at week 8 (exploratory analysis). Results: Overall, 169 pts withRAS WT mCRC were included in the ORR analysis and 154 had tumour-shrinkage data available at baseline and week 8. Significantly more pts in the pmab + mFOLFOX6 arm had ETS at week 8 vs. the bev + mFOLFOX6 arm (Table). ORRs were similar in the two arms, while DoR was significantly longer and DpR significantly greater with pmab + mFOLFOX6 (Table). ≥30% vs. &lt;30% tumour shrinkage at week 8 was associated with longer median PFS (HR: 0.52 [95% CI: 0.29–0.92] and HR: 0.65 [95% CI: 0.38–1.13]) and OS (HR: 0.44 [95% CI: 0.15–1.32] and HR: 0.23 [95% CI: 0.08–0.66]) for pmab + mFOLFOX6 and bev + mFOLFOX6, respectively. Conclusions: Although ORR appeared to be similar or only numerically improved in the pmab arm of PEAK, the responses observed appeared to occur earlier, last longer and be deeper in our exploratory analyses. This is consistent with the observed OS and PFS benefit, and with data reported earlier from the FIRE3 study. Clinical trial information: NCT00819780. [Table: see text]