Rechallenge with Anti-EGFR Treatment in RAS/BRAF wt Metastatic Colorectal Cancer (mCRC) in Real Clinical Practice: Experience of the GITuD Group

• Published in: Targeted oncology 2024-07, Vol.19 (4), p.565-573
• Main Authors: Salgado Fernández, Mercedes, Reboredo López, Margarita, Covela Rúa, Marta, Candamio, Sonia, González-Villarroel, Paula, Sánchez-Cousido, Luis Felipe, Graña, Begoña, Carral-Maseda, Alberto, Cameselle-García, Soledad, Varela Pose, Vanesa, Gallardo-Martín, Maria Elena, Martínez-Lago, Nieves
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Biomedicine; Cetuximab - pharmacology; Cetuximab - therapeutic use; Colorectal cancer; Colorectal Neoplasms - drug therapy; Colorectal Neoplasms - pathology; ErbB Receptors; Female; Humans; Male; Medicine; Medicine & Public Health; Metastasis; Middle Aged; Neoplasm Metastasis; Oncology; Original Research Article; Panitumumab - pharmacology; Panitumumab - therapeutic use; Proto-Oncogene Proteins B-raf - genetics; Retrospective Studies
• ISSN: 1776-2596; 1776-260X; 1776-260X
• DOI: 10.1007/s11523-024-01062-z

Background There are few third- and fourth-line therapeutic options for metastatic colorectal cancer (mCRC). In RAS/BRAF wild-type (wt) mCRC previously treated with anti-epidermal growth factor receptor (anti-EGFR) (first-line) and relapsed after a good response, retreatment with anti-EGFR (rechallenge) emerges as a therapeutic alternative. Objective The aim was to show the activity and safety of anti-EGFR rechallenge in RAS/BRAF wt mCRC in real-world practice. Patients and Methods A multicenter, retrospective, observational study (six hospitals of the Galician Group of Research in Digestive Tumors) was conducted. Adult patients with RAS/BRAF wt mCRC, evaluated by liquid biopsy, were included. They received anti-EGFR rechallenge (cetuximab, panitumumab) as monotherapy, or combined with chemotherapy, in third- or subsequent lines. Efficacy (overall response rate [ORR], disease control rate [DCR], overall survival [OS], and progression-free survival [PFS]) and safety (incidence of adverse events [AEs]) were assessed. Results Thirty-one patients were analyzed. Rechallenge (median 6 cycles [range 1–27], mainly cetuximab [80.7%]), started at a median anti-EGFR-free time of 18.4 months (1.7–37.5 months) after two (38.7%) or more (61.3%) lines of treatment; 64.5% of patients received a full dose. Median OS and PFS were 9.8 months (95% confidence interval [CI] 8.2–11.4) and 2.6 months (95% CI 1.7–3.4), respectively. ORR was 10%, and DCR was 30%. The most common AEs were diarrhea (35.5%), anemia (29%), emesis (6.4%), and neutropenia (6.4%);  1). Hypomagnesemia required supplements in 29% of patients. Dose delays (≥ 3 days) and reduction (≥ 20%) were reported in 11 (35.5%) and seven patients (22.6%), respectively. Conclusions In RAS/BRAF wt mCRC patients, an anti-EGFR rechallenge provides a feasible therapeutic option with clinical benefit (survival) and a manageable safety profile.