PURPOSE We assessed the prognostic/predictive role of primary tumor sidedness and uncommon alterations of anti–epidermal growth factor receptor (EGFR) primary resistance (primary resistance in RAS and BRAF wild-type metastatic colorectal cancer patients treated with anti-EGFR monoclonal antibodies [PRESSING] panel) in patients with RAS/BRAF wild-type (wt) metastatic colorectal cancer (mCRC) who were randomly assigned to panitumumab plus fluorouracil, leucovorin, and oxaliplatin (FOLFOX-4) induction followed by maintenance with panitumumab with or without fluorouracil (FU) plus leucovorin (LV); Valentino trial (ClinicalTrials.gov identifier: NCT02476045). PATIENTS AND METHODS This prespecified retrospective analysis included 199 evaluable patients with RAS/ BRAF wt. The PRESSING panel included the following: immunohistochemistry (IHC) and in situ hybridization for HER2/MET amplification, IHC with or without RNA sequencing for ALK/ROS1/NTRKs/RET fusions, next-generation sequencing for HER2/PIK3CAex.20/PTEN/AKT1 and RAS mutations with low mutant allele fraction, and multiplex polymerase chain reaction for microsatellite instability. PRESSING status (any positive biomarker v all negative) and sidedness were correlated with overall response rate (ORR), progression-free survival (PFS), and overall survival (OS) in the study population and by treatment arm. RESULTS Overall, left- and right-sided tumors were 85.4% and 14.6%, respectively, and PRESSING-negative and -positive tumors were 75.4% and 24.6%, respectively. At a median follow-up of 26 months, inferior outcomes were consistently observed in right- versus left-sided tumors for ORR (55.2% v 74.1%; P = .037), PFS (8.4 v 11.5 months; P = .026), and OS (2-year rate: 50.2% v 65.1%; P = .062). Similar results were observed in the PRESSING-positive versus PRESSING-negative subgroup for ORR (59.2% v 75.3%; P = .030), PFS (7.7 v 12.1 months; P, .001), and OS (2-year rate: 48.1% v 68.1%; P = .021). The PFS benefit of FU plus LV added to panitumumab maintenance, reported in the study, was independent from sidedness and PRESSING status (interaction for PFS P = .293 and .127, respectively). However, outcomes were extremely poor in patients who received single-agent panitumumab and had right-sided tumors (median PFS, 7.7 months; 2-year OS, 38.5%) or PRESSING-positive tumors (median PFS, 7.4 months; 2-year OS, 47.0%). CONCLUSION The combined assessment of sidedness and molecular alterations of anti-EGFR primary resistance identified a consistent proportion of patients with RAS/BRAF–wt mCRC who had inferior benefit from initial anti-EGFR–based regimens, particularly after maintenance with single-agent anti-EGFRs.
Negative hyperselection of patients with RAS and BRAF wild-type metastatic colorectal cancer who received panitumumab-based maintenance therapy / F. Morano, S. Corallo, S. Lonardi, A. Raimondi, C. Cremolini, L. Rimassa, R. Murialdo, A. Zaniboni, A. Sartore-Bianchi, G. Tomasello, P. Racca, M. Clavarezza, V. Adamo, F. Perrone, A. Gloghini, E. Tamborini, A. Busico, A. Martinetti, F. Palermo, F. Loupakis, M. Milione, G. Fuca, M. Di Bartolomeo, F. De Braud, F. Pietrantonio. - In: JOURNAL OF CLINICAL ONCOLOGY. - ISSN 0732-183X. - 37:33(2019 Nov 20), pp. 3099-3110.
|Titolo:||Negative hyperselection of patients with RAS and BRAF wild-type metastatic colorectal cancer who received panitumumab-based maintenance therapy|
DE BRAUD, FILIPPO GUGLIELMO MARIA (Penultimo)
PIETRANTONIO, FILIPPO (Ultimo) (Corresponding)
|Settore Scientifico Disciplinare:||Settore MED/06 - Oncologia Medica|
|Data di pubblicazione:||20-nov-2019|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1200/JCO.19.01254|
|Appare nelle tipologie:||01 - Articolo su periodico|