Abstract
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.
Original language | Undefined/Unknown |
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Pages (from-to) | 1017-1024 |
Number of pages | 8 |
Journal | Clinical cancer research : an official journal of the American Association for Cancer Research |
Volume | 26 |
DOIs | |
Publication status | Published - Mar 1 2020 |
Keywords
- Aged
- Antineoplastic Combined Chemotherapy Protocols
- therapeutic use
- Bevacizumab
- administration & dosage
- Biomarkers
- Tumor
- genetics
- metabolism
- Camptothecin
- Capecitabine
- Colorectal Neoplasms
- drug therapy
- pathology
- DNA Methylation
- DNA Modification Methylases
- DNA Repair Enzymes
- Female
- Fluorouracil
- Humans
- Irinotecan
- Leucovorin
- Male
- Middle Aged
- Oxaliplatin
- Proto-Oncogene Proteins p21(ras)
- Quality of Life
- Survival Rate
- Temozolomide
- Treatment Outcome
- Tumor Suppressor Proteins