530P - Real-world effectiveness and predictive biomarker analysis of TAS-102+bevacizumab vs. regorafenib vs. TAS-102 in metastatic colorectal cancer: A multicenter cohort study

Background

The SUNLIGHT trial has demonstrated superiority for TAS-102+bevacizumab (TAS-102+bev) over TAS-102 alone in patients with pretreated metastatic colorectal cancer (mCRC). However, real-world effectiveness data on TAS-102+bev are scarce. Moreover, recent studies have presented conflicting findings regarding efficacy of TAS-102±bev in patients with KRAS^G12 mutations. We aim to assess whether TAS-102+bev translates into improved outcomes compared to regorafenib (rego) or TAS-102 alone in a real-world setting and determine the predictive value of KRAS codon-specific mutations and other molecular subtypes for TAS-102+bev.

Methods

In this retrospective cohort study, patients with mCRC treated with TAS-102+bev, TAS-102 or rego at six cancer centers in Austria were included. The primary endpoint was progression-free survival, while co-secondary endpoints were disease control rate (DCR) and long-term response, defined as a PFS > 6 months. All patient data including molecular profiles were obtained by individual chart review.

Results

Overall, 471 patients were included: 122 patients were treated with TAS-102+bev, 201 with TAS-102 and 149 with rego. The median PFS (mPFS) was significantly longer with TAS-102+bev compared to TAS-102 and rego alone (mPFS, 4.1 vs. 2.8 vs. 2.8 months; p=0.003). Accordingly, patients treated with TAS-102+bev had a higher DCR (50% vs. 23% vs. 24%; p<0.001) and were more likely to have long-term response (29% vs. 15% vs. 14%; p=0.002) compared to TAS-102 and rego. Adjusting for potential confounders including age, ECOG performance status, tumor side, metastatic burden, and line of therapy the risk of progression remained significantly lower for TAS-102+bev compared with TAS-102 (Hazard ratio (HR); 0.65, 95% Confidence Interval (CI) 0.45 – 0.91; p=0.013) and rego (HR: 0.67, CI 0.45-0.99; p=0.045). Notably, the PFS benefit with TAS-102+bev was independent of the RAS, KRAS^G12, KRAS^G13, PIK3CA and TP53 mutational status (p values from interaction tests all >0.1).

Conclusions

This study indicates that TAS-102+Bev has increased real-world effectiveness compared to TAS-102 and regorafenib alone across key molecular subgroups.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

F. Huemer: Financial Interests, Speaker, Consultant, Advisor: Servier. J.M. Riedl: Financial Interests, Personal, Speaker, Consultant, Advisor: Servier; Financial Interests, Personal, Research Funding: Servier. All other authors have declared no conflicts of interest.