Efficacy of third-line anti-EGFR-based treatment versus regorafenib or trifluridine/tipiracil according to primary tumor site in RAS/BRAF wild-type metastatic colorectal cancer patients

• Published in: Frontiers in oncology Vol. 13; p. 1125013
• Main Authors: Salvatore, Lisa, Bensi, Maria, Vivolo, Raffaella, Zurlo, Ina Valeria, Dell'Aquila, Emanuela, Grande, Roberta, Anghelone, Annunziato, Emiliani, Alessandra, Citarella, Fabrizio, Calegari, Maria Alessandra, Ribelli, Marta, Basso, Michele, Pozzo, Carmelo, Tortora, Giampaolo
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 21.02.2023
• Subjects: anti-egfr ab; colorectal cancer; Oncology; primary tumor site; RAS/BRAF wild-type; Regorafenib; third-line therapy; third-line therapy; Regorafenib; colorectal cancer; anti-egfr ab; RAS/BRAF wild-type; primary tumor site; trifluridine/tipiracil
• ISSN: 2234-943X; 2234-943X
• DOI: 10.3389/fonc.2023.1125013

Right- (R) and left-sided (L) metastatic colorectal cancer (mCRC) exhibit different clinical and molecular features. Several retrospective analyses showed that survival benefit of anti-EGFR-based therapy is limited to RAS/BRAF wt L-sided mCRC patients. Few data are available about third-line anti-EGFR efficacy according to primary tumor site. RAS/BRAF wt patients mCRC treated with third-line anti-EGFR-based therapy versus regorafenib or trifluridine/tipiracil (R/T) were retrospectively collected. The objective of the analysis was to compare treatment efficacy according to tumor site. The primary endpoint was progression-free survival (PFS); secondary endpoints were overall survival (OS), response rate (RR) and toxicity. A total of 76 RAS/BRAF wt mCRC patients, treated with third-line anti-EGFR-based therapy or R/T, were enrolled. Of those, 19 (25%) patients had a R-sided tumor (9 patients received anti-EGFR treatment and 10 patients R/T) and 57 (75%) patients had a L-sided tumor (30 patients received anti-EGFR treatment and 27 patients R/T). A significant PFS [7.2 vs 3.6 months, HR 0.43 (95% CI 0.2-0.76), p= 0.004] and OS benefit [14.9 vs 10.9 months, HR 0.52 (95% CI 0.28-0.98), p= 0.045] in favor of anti-EGFR therapy vs R/T was observed in the L-sided tumor group. No difference in PFS and OS was observed in the R-sided tumor group. A significant interaction according to primary tumor site and third-line regimen was observed for PFS (p= 0.05). RR was significantly higher in L-sided patients treated with anti-EGFR vs R/T (43% vs. 0%; p <0.0001), no difference was observed in R-sided patients. At the multivariate analysis, third-line regimen was independently associated with PFS in L-sided patients. Our results demonstrated a different benefit from third-line anti-EGFR-based therapy according to primary tumor site, confirming the role of L-sided tumor in predicting benefit from third-line anti-EGFR vs R/T. At the same time, no difference was observed in R-sided tumor.