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

• Published in: The oncologist (Dayton, Ohio) Ohio), 2022-02, Vol.27 (1), p.e29-e36
• Main Authors: Fucà, Giovanni, Raimondi, Alessandra, Prisciandaro, Michele, Lonardi, Sara, Cremolini, Chiara, Ratti, Margherita, Clavarezza, Matteo, Murialdo, Roberto, Sartore-Bianchi, Andrea, Smiroldo, Valeria, Berenato, Rosa, Racca, Patrizia, Bergamo, Francesca, Corallo, Salvatore, Di Bartolomeo, Maria, de Braud, Filippo, Morano, Federica, Pietrantonio, Filippo
• Format: Article
• Language: English
• Subjects: Antineoplastic Combined Chemotherapy Protocols; Care and treatment; Colonic Neoplasms - drug therapy; Colorectal Neoplasms - drug therapy; Colorectal Neoplasms - genetics; Diagnosis; Gastrointestinal Cancer; Humans; Metastasis; Panitumumab - pharmacology; Prospective Studies; Proto-Oncogene Proteins B-raf - genetics; Rectal Neoplasms - drug therapy
• ISSN: 1083-7159; 1549-490X
• DOI: 10.1093/oncolo/oyab012

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. 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. 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. 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.