Early tumor shrinkage (ETS) as clinical factor to select maintenance with cetuximab (cet) monotherapy in patients (pts) with RAS/BRAF wild-type (wt) metastatic colorectal cancer (mCRC): A secondary endpoint analysis of the ERMES study.

Abstract

3603 Background: ERMES study aimed to demonstrate non-inferior PFS of maintenance with cetuximab (cet) monotherapy (arm B) compared to FOLFIRI+cet until progression (arm A) in RAS and BRAF wt mCRC pts. Although study did not meet its primary endpoint it showed better toxicity profile and OS for cet alone and comparable ORR between arms. Here we present results of ETS, a secondary endpoint. Methods: ETS was defined as ≥20% reduction of the sum of target lesions at 8 weeks from the start of treatment, and was assessed by blinded independent central review. PFS and OS were compared between ETS+ and ETS- pts according to treatment arm in the modified Per-Protocol (mPP) population. Results: 327 of 337 (97%) pts were evaluable for ETS. In arm A, no statistically significant differences were observed between ETS+ and ETS- cohort for PFS (11.9 m, 95%CI 11.28-13.19, vs 12.2 m, 95%CI 10.82-14.93; HR 1.05, 95%CI 0.73-1.50; p 0.77) and OS (30.75 m, 95%CI 25.09-37.73, vs 25.46 m, 95%CI 19.96-34.63; HR: 0.79, 95%CI 0.50-1.24; p 0.29). In arm B, a statistically significant difference was observed between ETS+ and ETS- cohort for PFS (10.62 m, 95%CI 9.86-13.09, vs 8.52 m, 95%CI 7.89-9.37; HR 0.70, 95%CI 0.49-1.00; p 0.036) and for OS (38.88 m, 95%CI 34.53-43.25, vs27.43 m, 95%CI 20.59-36.64; HR 0.60, 95%CI 0.38-0.93; p 0.019). ETS+ pts reported no statistically significant difference between arm B and arm A in terms of PFS (HR 1.12, 95%CI 0.83-1.49; p 0.43) while experiencing a better OS for arm B compared to arm A (HR 0.72, 95%CI 0.50-1.05; p 0,08). Conclusions: In pts achieving ETS, induction treatment with FOLFIRI+cet may be de-escalated to cet alone without detrimental effect on PFS, resulting in less toxicity and better OS. These data support the hypothesis that ETS might be a clinical dynamic predictor of efficacy of a less intensive maintenance strategy, allowing to plan de-escalation to cet alone after 4 months of FOLFIRI+cet induction. Clinical trial information: NCT02484833 .