Reinduction of an Anti-EGFR-based First-line Regimen in Patients with RAS Wild-type Metastatic Colorectal Cancer Enrolled in the Valentino Study

Background
In patients with RAS/BRAF wild-type metastatic colorectal cancer (mCRC), growing evidence supports anti-epidermal growth factor receptor (EGFR) retreatment, whereas little is known on the outcomes of anti-EGFR-based reinduction therapy during the upfront strategy.

Methods
We included patients enrolled in the Valentino study who had disease progression and received at least one dose of post-progression therapy. The Kaplan–Meier method and Cox proportional hazards regression were used for the survival analysis. When comparing the outcomes of anti-EGFR-based reinduction versus any second line, a propensity score–based matching was used.

Results
Liver-limited/single site of disease (P < .001 and P = .002), left-sidedness (P = .029), surgery of metastases (P = .003), early tumor shrinkage, and deeper responses (P = .018 and P = .036) were associated with the use of anti-EGFR-based reinduction versus any other second line. All patients treated with reinduction had an anti-EGFR-free interval of at least 3 months. In the propensity score–matched population, progression-free survival (PFS) was similar in the 2 treatment groups, the overall survival (OS) was significantly longer for patients treated with reinduction (P = .029), and the response rate was higher in patients treated with reinduction (P = .033). An oxaliplatin-free interval ≥12 months, left-sidedness, and molecular hyperselection beyond RAS/BRAF were associated with significantly better outcomes after anti-EGFR-based reinduction.

Conclusions
Reinduction strategies with anti-EGFR-based regimens are commonly used in clinical practice. Our data highlight the importance of clinical–molecular selection for re-treatments and the need for prospective strategy trials in selected populations.