Phase II trial of capecitabine plus erlotinib versus capecitabine alone in patients with advanced colorectal cancer

Aim & methods: Capecitabine monotherapy as palliation for advanced colorectal cancer (CRC) is generally well tolerated. Adding erlotinib, an EGFR-tyrosine kinase inhibitor, might improve efficacy versus capecitabine alone. 82 patients received capecitabine alone (Arm 1) or capecitabine with erlotinib (Arm 2). Results: Median time-to-progression (TTP) in Arm 1 was 7.9 months versus 9.2 in Arm 2. In KRAS-wild type (WT) patients TTP was 8.4 and 11.7 months in Arms 1 and 2, respectively. In KRAS-mutated patients TTP was 7.4 and 1.9 months in Arms 1 and 2, respectively (p = 0.023). Arm 2 KRAS-WT patients, left-sided primaries, had an overall survival of 16.0 versus 12.1 months in right-sided primaries. Conclusion: Adding erlotinib to capecitabine increased TTP by 3.2 months in KRAS-WT patients. This study suggests that erlotinib harms patients with KRAS-mutated advanced CRC while it may provide benefit to those with KRAS-WT CRC. Further study of EGFR-tyrosine kinase inhibitors in patients with left-sided KRAS-WT CRC is warranted.