Primary tumor sidedness and negative hyperselection to modulate anti-EGFR-based maintenance strategies in patients with RAS wild-type metastatic colorectal cancer: individual patient data pooled analysis of two randomized clinical trials
Year: 2025
Type: article
Abstract: 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. Patients with RAS WT mCRC received FOLFOX plus Panitumumab induction therapy followed by maintenance with 5-fluorouracil/leucovorin (5-FU/LV) plus Panitumumab vs. 5-FU/LV monotherapy (PanaMa) or Panitumumab monotherapy (Valentino). Outcomes included progression-free survival (PFS) and overall survival (OS). Subgroup analyses examined primary tumor sidedness (left vs. right) and hyperselection status (negative vs. altered). RESULTS: Among 607 patients receiving induction, sidedness and hyperselection status were available for 589 and 511 patients, respectively. Left-sided and negative hyperselected tumors were observed in 80.2% and 63.9% of patients, respectively. Panitumumab-based maintenance improved PFS in left-sided, negative hyperselected patients compared to 5-FU/LV alone, with no OS differences. PFS and OS were comparable for Panitumumab alone vs. Panitumumab plus 5-FU/LV. CONCLUSION: Tumor sidedness and hyperselection status significantly influence maintenance strategy efficacy in mCRC. For left-sided, negative hyperselected patients, Panitumumab monotherapy may optimize efficacy while minimizing toxicity. Further investigation into the relative contribution of individual hyperselection parameters in this setting is warranted.
Source: British Journal of Cancer
Authors: Alexej Ballhausen, Federica Morano, Arndt Stahler, Sara Lonardi, Andreas Jay Kind, Chiara Cremolini, Susanna Swoboda, Giovanni Randon, David Horst, Michele Prisciandaro, Annabel Helga Sophie Alig, Chiara Carlotta Pircher, Armin Jarosch, Paola Andena, Annika Kurreck, Anna Alessandra Chiaramonte, Sebastian Stintzing, Filippo Pietrantonio, Dominik Paul Modest, Alessandra Raimondi
Institutions: Humboldt-Universität zu Berlin, Freie Universität Berlin, Charité - Universitätsmedizin Berlin, Fondazione IRCCS Istituto Nazionale dei Tumori, Istituto Oncologico Veneto, University of Pisa, Azienda Ospedaliera Universitaria Pisana, German Cancer Research Center, Deutsches Konsortium für Translationale Krebsforschung
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $5,190
OpenAlex ID: W4413770238