98%
921
2 minutes
20
Background: Metastatic colorectal cancer (mCRC) treatment has been evolving and increasingly driven by tumor biology and gene expression analysis. Rechallenge with epidermal growth factor receptor (EGFR) inhibitors (anti-EGFR) represents a promising strategy for patients with RAS wild-type (RAS-wt) mCRC and circulating tumor DNA has emerged as a potential selection strategy. Herein, we report the case of a RAS-wt mCRC patient who had a successful response to cetuximab rechallenge.
Case Summary: Our patient was diagnosed with stage IV RAS-wt, microsatellite-stable rectosigmoid junction adenocarcinoma. He was started on first-line treatment with FOLFIRI and cetuximab and achieved partial response, allowing for a left hepatectomy (R0), followed by post-operative chemotherapy and an anterior resection; progression-free survival (PFS) of 16 months was obtained. Due to hepatic and nodal relapse, second-line treatment with FOLFOX and bevacizumab was started with partial response; metastasectomy was performed (R0), achieving a PFS of 11 months. After a 15 months anti-EGFR-free interval, FOLFIRI and cetuximab were reintroduced upon disease progression, again with partial response and a PFS of 16 months. Following extensive hepatic relapse, cetuximab was reintroduced and a marked clinical and analytical improvement was seen, after only one cycle. RAS-wt status was confirmed on circulating tumor DNA. The patient's overall survival exceeded 5 years.
Conclusion: Our case provides real-world data to support cetuximab rechallenge in later lines of RAS-wt mCRC treatment.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11438852 | PMC |
http://dx.doi.org/10.5306/wjco.v15.i9.1232 | DOI Listing |
Int J Cancer
September 2025
Medical Department, iOMEDICO, Freiburg, Germany.
Existing prognostic scores for metastatic colorectal cancer (mCRC) are based on randomized clinical trial data and focus on parameters evaluated at the start of first-line (1L) treatment. Unlike these, the modified mCRC prognostic score (mCCS) was developed using real-world data from the German tumor registry colorectal cancer (TKK) and is based on pre-1L treatment information. It predicts overall survival (OS) for patients with RAS-wild-type (WT) mCRC using five tumor characteristics identified as independent negative prognostic factors.
View Article and Find Full Text PDFBr J Cancer
August 2025
Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
Background: Patients with RAS wild-type (WT), left-sided metastatic colorectal cancer (mCRC), negatively hyperselected for anti-EGFR resistance alterations, benefit most from anti-EGFR-based first-line treatment. The predictive impact of these stratification parameters on maintenance strategy efficacy is unclear.
Methods: This pooled analysis included individual patient data from the PanaMa (NCT01991873) and Valentino (NCT02476045) phase 2 trials.
Purpose: Tumor immune cell infiltration patterns in the tumor microenvironment serve as prognostic biomarkers in metastatic colorectal cancer (mCRC). This study analyzed the spatially resolved tumor immune microenvironment for prognostic and predictive impact in patients with RAS wildtype mCRC receiving FU/FA ± Pmab maintenance after Pmab + FOLFOX induction (PanaMa AIO KRK0212; NCT01991873).
Patients And Methods: Twelve immune parameters (lymphocyte markers: CD3, CD8, CD45RO, FOXP3, CD20, Granzyme B, Perforin; immune checkpoints: PD-1, PD-L1, IDO1, LAG3; monocyte marker CD163) were quantified in spatially resolved tumor and stroma regions (invasive-margin [Inv], center [Cen]) on tissue microarrays from available surgical resections using digital pathology.
Crit Rev Oncol Hematol
July 2025
Clinical Oncology Unit, Careggi University Hospital, Florence, Italy; Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy; Department of Health Science, University of Florence, Florence, Italy.
Metastatic colorectal cancer (mCRC) remains a major clinical challenge, despite therapeutic advancements. Mutations in KRAS and NRAS (RAS) oncogenes drive resistance to anti-EGFR drugs, necessitating RAS mutational analysis prior to treatment. While tissue biopsy remains the gold standard for molecular profiling, it has limitations such as invasiveness, intra-tumoral heterogeneity, and delayed results.
View Article and Find Full Text PDFCancers (Basel)
March 2025
Department of Experimental Medicine, Sapienza University, 00161 Rome, Italy.
: In metastatic colorectal cancer (mCRC), liquid biopsy has enabled the identification of "neo-RAS-Wild-Type (WT)", a transient phase characterized by the disappearance of RAS mutations, with significant clinical implications for re-sensitization to EGFR blockade. This study aimed to prospectively track the kinetics of neo-RAS-WT in circulating tumor DNA (ctDNA) among RAS-mutant mCRC patients receiving first-line and subsequent systemic therapies. : A total of 380 serial blood samples from 35 patients were analyzed.
View Article and Find Full Text PDF