Purpose: To determine whether second-line therapy with cape citabine and temozolomide was superior to irinotecan, leucovorin, and fluorouracil (FOLFIRI) in patients with RAS-mutated, methyl guanine methyltransferase (MGMT)-methylated metastatic colo rectal cancer (mCRC). Patients and Methods: In this randomized, phase II trial, we enrolled patients with RAS-mutated, MGMT-methylated mCRC after failure of oxaliplatin-based regimen. Patients with centrally confirmed MGMT methylation were stratified by first-line progres sion-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. Results: Between November 2014 and May 2019, 86 patients were randomly assigned to arm A (n ¼ 43) or arm B (n ¼ 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 P ¼ 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 ¼ 1.19 (0.82–1.72) and HR ¼ 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. Conclusions: Temozolomide-based therapy warrants further investigation in molecularly hyperselected subgroups.
Capecitabine and Temozolomide versus FOLFIRI in RAS-Mutated, MGMT-Methylated Metastatic Colorectal Cancer
Corallo S;
2020-01-01
Abstract
Purpose: To determine whether second-line therapy with cape citabine and temozolomide was superior to irinotecan, leucovorin, and fluorouracil (FOLFIRI) in patients with RAS-mutated, methyl guanine methyltransferase (MGMT)-methylated metastatic colo rectal cancer (mCRC). Patients and Methods: In this randomized, phase II trial, we enrolled patients with RAS-mutated, MGMT-methylated mCRC after failure of oxaliplatin-based regimen. Patients with centrally confirmed MGMT methylation were stratified by first-line progres sion-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. Results: Between November 2014 and May 2019, 86 patients were randomly assigned to arm A (n ¼ 43) or arm B (n ¼ 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 P ¼ 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 ¼ 1.19 (0.82–1.72) and HR ¼ 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. Conclusions: Temozolomide-based therapy warrants further investigation in molecularly hyperselected subgroups.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
