Details

Autor(en) / Beteiligte

• Pietrantonio, Filippo
• Lobefaro, Riccardo
• Antista, Maria
• Lonardi, Sara
• Raimondi, Alessandra
• Morano, Federica
• Mosconi, Stefania
• Rimassa, Lorenza
• Murgioni, Sabina
• Sartore-Bianchi, Andrea
• Tomasello, Gianluca
• Longarini, Raffaella
• Farina, Gabriella
• Petrelli, Fausto
• Gori, Stefania
• Randon, Giovanni
• Corallo, Salvatore
• Pagani, Filippo
• Guarini, Vincenzo
• Palermo, Federica
• Martinetti, Antonia
• Macagno, Marco
• Barault, Ludovic
• Perrone, Federica
• Tamborini, Elena
• Milione, Massimo
• Di Nicolantonio, Federica
• Di Maio, Massimo
• Fucà, Giovanni
• Di Bartolomeo, Maria
• de Braud, Filippo

Titel

Capecitabine and Temozolomide versus FOLFIRI in RAS-Mutated, MGMT-Methylated Metastatic Colorectal Cancer

Ist Teil von

• Clinical cancer research, 2020-03, Vol.26 (5), p.1017-1024

Ort / Verlag

United States

Erscheinungsjahr

2020

Quelle

MEDLINE

Beschreibungen/Notizen

• To determine whether second-line therapy with capecitabine and temozolomide was superior to irinotecan, leucovorin, and fluorouracil (FOLFIRI) in patients with -mutated, methyl-guanine methyltransferase ( )-methylated metastatic colorectal cancer (mCRC). In this randomized, phase II trial, we enrolled patients with -mutated, -methylated mCRC after failure of oxaliplatin-based regimen. Patients with centrally confirmed methylation were stratified by first-line progression-free survival (PFS) and prior bevacizumab and randomized to either capecitabine plus temozolomide (arm A, CAPTEM) or FOLFIRI (arm B). The primary endpoint was PFS analyzed on intention-to-treat basis, with 90% power and one-sided significance level of 0.05 to detect an increase of median time from 2 months in arm B to 4 months in arm A. Between November 2014 and May 2019, 86 patients were randomly assigned to arm A ( = 43) or arm B ( = 43). After a median follow-up of 30.5 months (interquartile range, 12.2-36.3), 79 disease progression or death events occurred. Superiority of arm A was not demonstrated (one-sided = 0.223). Progression-free survival and overall survival were 3.5 (2.0-5.0) and 9.5 (8.2-25.8) in arm A versus 3.5 (2.3-6.1) and 10.6 (8.5-20.8) in arm B [HR = 1.19 (0.82-1.72) and HR = 0.97 (0.58-1.61)], respectively. Grade ≥3 treatment-related adverse events had higher incidence in arm B versus A (47.6% vs 16.3%), and quality of life was significantly worse in arm B. Patients with positive MGMT expression by IHC did not benefit from CAPTEM. Temozolomide-based therapy warrants further investigation in molecularly hyperselected subgroups.