396P Impact of depth of response of induction therapy on consecutive maintenance therapy in patients with RAS wild-type metastatic colorectal cancer: An analysis of the PanaMa trial (AIO KRK 0212)

Abstract

Depth of response (DpR) is associated with improved progression-free survival (PFS) and overall survival (OS) in patients with RAS wild-type (WT) metastatic colorectal cancer (mCRC). There are limited data on the relevance of DpR to induction therapy for consecutive maintenance treatment. Thus, the impact of DpR to induction with 6 cycles of 5-fluoruracil/leucovorin (FU/FA), oxaliplatin and panitumumab (pmab) on the efficacy of maintenance therapy with pmab-FU/FA vs. FU/FA alone was examined within the randomized PanaMa trial. Computed tomography and magnetic resonance imaging were used for central radiologic assessment. DpR was defined as change of tumor diameter from baseline 1 (pre-induction) to baseline 2 (post-induction). Cox regression models and log-rank tests estimated hazard ratios including 95% confidence intervals of DpR (grouped as DpR 1= <0-30%; DpR 2= >30-50%; DpR 3= >50-100%) on PFS and OS during maintenance therapy. Out of 248 patients in the full analysis set 211 were evaluable for central review and DpR analysis (arm A, n=106; arm B, n=105). Median DpR was similar in both treatment arms (42.7% [arm A] vs. 42.2% [arm B]). Cox regression analysis demonstrated a significant correlation of initial DpR with both consecutive PFS (p=0.023) and OS (p=0.046) in the pmab-arm while in patients receiving FU/FA alone this association was not observed. There was no predictive value of DpR groups on efficacy according to treatment arm.Table: 396PFU/FA+pmab (n=106)FU/FA (n=105)DpR 1<0-30%DpR 2>30-50%DpR 3>50-100%DpR 1<0-30%DpR 2>30-50%DpR 3>50-100%Patients (n)215233205233Median PFS, months (95% CI)8.1 (2.7-13.5)9.9 (6.8-13.1)9.5 (5.5-13.5)5.2 (4.6-5.8)5.8 (4.9-6.7)6.1 (4.2-8.1)HR (95% CI), p (log-rank)-0.57 (0.35-1.02)0.43 (0.24-0.80)-0.69 (0.40-1.18)0.60 (0.33-1.08)p=0.023p=0.213Median OS, months (95% CI)16.4 (12.2-20.6)28.2 (23.9-32.5)27.4 (21.1-33.8)17.1 (14.9-19.4)26.4 (22.4-30.5)28.1 (22.9-33.4)HR (95% CI), p (log-rank)-0.50 (0.26-0.94)0.46 (0.23-0.92)-0.52 (0.26-1.303)0.40 (0.18-0.87)p=0.046p=0.054 Open table in a new tab In RAS WT mCRC treated within in the PanaMa trial, DpR to induction therapy has a prognostic impact on subsequent maintenance treatment. This effect appears pronounced in patients receiving pmab-based maintenance therapy.