388P Early tumor shrinkage (ETS) and depth of response (DpR) analyses in metastatic colorectal cancer (mCRC) treated with first-line mFOLFOX6 plus panitumumab (PAN) or bevacizumab (BEV): Results from the phase III PARADIGM trial

Abstract

The PARADIGM primary analysis demonstrated that PAN significantly improved OS vs BEV combined with mFOLFOX6 in RAS WT and left-sided mCRC. ETS and DpR are on-treatment prognostic factors related to favorable OS and PFS in mCRC chemotherapy. We report ETS and DpR and the correlation with OS and PFS in patients (pts) with RAS WT mCRC from PARADIGM. Relative change in maximum tumor diameter was analyzed between baseline and 8 wks of treatment. ETS was defined as a ≥30% decrease in tumor size by investigator assessment. OS and PFS were compared in pts with/without ETS stratified by treatment arm and primary tumor location (left-sided, overall, right-sided). DpR was the maximum post-baseline percent decrease in the sum diameter of target lesions. No hypothesis was formally tested; P-values were based on a 2-sided stratified log-rank test and were descriptive. Cutoff date: Jan 14, 2022. A greater proportion of pts had ETS with PAN (left: 64.4%; overall: 58.5%) vs BEV (left: 38.0%; overall: 38.8%). Left-sided PAN pts with ETS showed longer OS (median: 42.6 vs 27.1 mo; HR: 0.56 [95% CI: 0.42–0.75]; P<0.001) and PFS (15.7 vs 9.6 mo; 0.62 [0.48–0.81]; P<0.001) than pts without ETS. Similarly, left-sided BEV pts with ETS had longer OS (median: 41.3 vs 32.4 mo; HR: 0.69 [95% CI: 0.52–0.91]; P=0.01) and PFS (14.5 vs 11.5 mo; 0.81 [0.62–1.06]; P=0.094). Right-sided PAN pts with ETS had longer OS, but not BEV (Table). Left-sided and overall PAN groups had greater median DpR than BEV (left, -59.4 vs -43.6; overall, -57.3 vs -43.6), with no difference between right-sided arms. Although ETS was associated with favorable survival outcomes in both arms, PAN achieved more ETS and greater DpR than BEV in left-sided pts. In right-sided pts, ETS was only predictive with PAN, warranting further biomarker analysis to predict PAN benefit.Table: 388POSPAN + mFOLFOX6BEV + mFOLFOX6ETS ≥30%ETS <30%ETS ≥30%ETS <30%Leftn=201n=111n=111n=181Median (95% CI), mo42.6 (37.5–49.7)27.1 (21.8–36.3)41.3 (31.6–46.5)32.4 (27.9–36.8)HR 95% CI P value0.56 0.42–0.75 <0.0010.69 0.52–0.91 0.010Overalln=234n=166n=156n=246Median (95% CI), mo42.1 (37.5–48.4)23.1 (17.7–31.0)33.8 (29.3–41.3)30.5 (26.9–34.0)HR 95% CI P value0.50 0.39–0.64 <0.0010.78 0.62–0.99 0.036Rightn=30n=54n=42n=61Median (95% CI), mo34.1 (21.0–42.2)15.2 (11.3–20.2)22.3 (17.4–30.9)25.5 (16.9–31.6)HR 95% CI P value0.47 0.28–0.79 0.0050.94 0.60–1.45 0.746 Open table in a new tab