Propensity score–matched analysis of trifluridine-tipiracil plus bevacizumab (FTD/TPI+Bev) vs anti-EGFR re-treatment in pretreated metastatic colorectal cancer (mCRC).

3581 Background: The SUNLIGHT trial established FTD/TPI+Bev as a preferred 3rd-line option for unselected mCRC patients (pts). Recently, the phase II randomized PARERE trial reported high response rates and favorable progression-free survival (PFS) with anti-EGFR re-treatment in RAS/BRAF wild-type (wt) mCRC pts selected by liquid biopsy versus regorafenib. In the absence of head-to-head comparisons between these two strategies, we performed an indirect analysis, using propensity score matching (PSM) to minimize baseline imbalances. Methods: Two cohorts of pretreated (≥2 previous lines) mCRC pts were compared: pts with RAS/BRAF wt tumors receiving FTD/TPI+Bev enrolled in the Italian real-world FLOWER trial, and RAS/BRAF wt pts at the liquid biopsy enrolled in Arm A (panitumumab (Pan) re-treatment followed by regorafenib) of the PARERE trial. PSM was applied adjusting for age, sex, ECOG performance status, number (N) of metastatic sites, N of prior treatment lines, tumor sidedness, and presence of liver and peritoneal metastases. Results: Overall, 75 pts treated with FTD/TPI+Bev and 103 pts treated with Pan were included. In the unmatched populations, median PFS was 6.0 months with FTD/TPI+Bev vs 4.1 months with Pan (p<0.001). Median OS was 13.6 months and 11.6 months, respectively (p=0.756). ORR was 9.3% with FTD/TPI+Bev and 16.5% with Pan (p=0.172). After PSM, 68 pts per cohort were analyzed. Median PFS was 5.0 months with FTD/TPI+Bev vs 3.9 months with Pan [HR 1.65 (95% CI, 1.14-2.38), p=0.007]. Median OS was 13.1 months vs 11.6 months, respectively [HR: 0.89 (95% CI: 0.59-1.34); p=0.569]. ORR remained numerically higher in the Pan group, although not statistically significant (p=0.34). Results were consistent regardless of N of anti-EGFR-free lines [1 vs ≥2; HR for PFS: 0.85 (95% CI: 0.58-1.23), p=0.379; HR for OS 0.85 (95% CI: 0.56-1.29), p=0.446], type of prior anti-EGFR therapy [Pan vs Cetuximab; HR for PFS: 0.80 (95% CI: 0.58-1.10), p=0.163; HR for OS 0.87 (95% CI: 0.61-1.24), p=0.435], and response to previous anti-EGFR treatment [HR for PFS: 0.87 (95% CI: 0.59-1.28), p=0.485; HR for OS 0.80 (95% CI: 0.59-1.28), p=0.279]. Toxicity profiles differed between treatments: neutropenia (any grade (G) 52% vs 3%; G3-4: 37% vs 1%), anemia (39% vs 15%; G3-4: 5% vs 1%), nausea (25% vs 10%; G3-4: 4% vs 0%), thrombocytopenia (24% vs 7%; G3-4: 4% vs 0%) and hypertension (21% vs 1%; 4% vs 0%) were more frequent with FTD/TPI+Bev, whereas rash occurred exclusively in the Pan group (81%; G3-4: 19%). Conclusions: Although underpowered, this indirect comparison suggests that FTD/TPI+Bev may achieve longer PFS than Pan re-treatment in pretreated mCRC pts, while anti-EGFR rechallenge may be associated with numerically higher response rate, with no OS difference. Prospective randomized trials are warranted to confirm these findings.