Anti-EGFR (Micromedmark Biotech)

Aflibercept (AFL) plus FOLFIRI prolongs overall survival (OS) in patients with metastatic colorectal cancer (mCRC). However, there is limited evidence on the efficacy and safety of AFL plus FOLFIRI previously treated with anti‐epidermal growth factor receptor (EGFR) agents. Therefore, we conducted a prospective open‐label phase II trial evaluating the efficacy and safety of AFL plus FOLFIRI in Japanese patients with mCRC failing a prior oxaliplatin‐based chemotherapy plus an anti‐EGFR agent. AFL (4 mg/kg iv) followed by FOLFIRI (irinotecan 180 mg/m2, leucovorin 200 mg/m2 iv, bolus 5‐fluorouracil [5‐FU] 400 mg/m2, and infusional 5‐FU 2400 mg/m2/46 h) was given every 2 weeks until progression or unacceptable toxicities. The primary endpoint was progression‐free survival (PFS) rate at 6 months. Forty three patients were enrolled between November 2019 and October 2022. The primary endpoint was met: 6‐month PFS rate was 58.8% (90% confidence interval [CI], 45.7%–72.0%). Median PFS and OS were 7.3 months (95% CI, 5.5–11.0 months) and 18.8 months (95% CI, 12.9–26.6 months), respectively. The overall response rate was 20.9% (95% CI, 10.0–36.0%) and disease control rate was 88.4% (95% CI, 74.9–96.1%). The main grade ≥3 adverse events included hypertension (62.8%), neutropenia (55.8%), leukopenia (25.6%), febrile neutropenia (11.6%), fatigue (9.3%), anorexia (9.3%), proteinuria (9.3%), and diarrhea (7.0%). No deaths and no new safety signals with a causal relation to the study treatment were observed. This study suggests that AFL plus FOLFIRI shows a high response rate and a manageable safety profile in Japanese patients with mCRC who failed prior oxaliplatin‐based chemotherapy plus an anti‐EGFR agent.

Bevacizumab and antiepidermal growth factor receptor-blocking (anti-EGFR) agents plus chemotherapy are first-line therapies for metastatic colorectal cancer (mCRC). Conversion surgery may improve outcomes; however, the extent to which it explains the difference in mortality rates among treatments is unclear. Herein, we aimed to assess the effects of conversion surgery on survival outcomes of patients with unresectable mCRC treated with bevacizumab and anti-EGFR agents.

This retrospective cohort study included patients with mCRC treated with bevacizumab and anti-EGFR agents as first-line therapy. We estimated the direct and indirect effects of treatments by comparing the mortality risk associated with targeted therapy type. Hazard ratios (HR) and the corresponding confidence intervals (CI) were estimated. Mediation analysis was used to estimate hazard ratio differences, and the proportion mediated.

A total of 5,106 patients were included. The natural indirect effect of conversion surgery reduced mortality risk (HR: 0.95; 95% CI, 0.93-0.97), with a mediated proportion of 42% after propensity score adjustment. In subgroup analyses, KRAS wild-type (HR: 0.94; 95% CI: 0.91-0.97), left tumor sidedness (HR: 0.94; 95% CI, 0.91-0.96), and liver resection (HR: 0.95; 95% CI, 0.93-0.98) were associated with reduced risks of mortality. The controlled and total direct effects of targeted therapy were associated with reduced mortality risk in the anti-EGFR-treated group compared to those in the bevacizumab-treated group; however, this effect was not statistically significant.

Conversion surgery may account for the difference in survival outcomes between users of the anti-EGFR agents and bevacizumab.