Sequential therapy with bevacizumab and EGFR inhibitors for metastatic colorectal carcinoma: a national registry-based analysis

Abstract

Although inhibitors of vascular endothelial growth factor and inhibitors of epidermal growth factor receptor (EGFRi) are commonly used for the treatment of metastatic colorectal cancer (mCRC), the optimal sequencing of these agents is currently unclear. Methods: A national registry of targeted therapies was used to analyze baseline characteristics and outcomes of patients with mCRC and wild-type KRAS exon 2 status who received bevacizumab and EGFRi (cetuximab or panitumumab) as a part of first-and second-line treatment in either sequence. Results: The cohort included 490 patients (181 patients treated with first-line EGFRi and second-line bevacizumab and 309 patients treated with first-line bevacizumab and second-line EGFRi). Median overall survival (OS) from the initiation on first-line therapy was similar for patients treated with either sequence, reaching 31.8 (95% CI 27.5-36.1) vs 31.4 months (95% CI 27.8-35.0) for EGFRi → bevacizumab vs bevacizumab → EGFRi cohort, respectively. Time from first-line initiation to progression on the second-line therapy [progression-free survival (PFS)] was 21.1 (95% CI 19.3-23.0) vs 19.3 months (95% CI 17.3-21.3) for bevacizumab → EGFRi vs EGFRi → bevacizumab cohort, respectively (P=0.016). Conclusion: This retrospective analysis of real-world data of patients with wild-type KRAS exon 2 mCRC showed no differences in OS between cohorts treated with bevacizumab → EGFRi vs the reverse sequence while combined PFS favored the bevacizumab → EGFRi sequence.

<p>Regorafenib for Metastatic Colorectal Cancer: An Analysis of a Registry-Based Cohort of 555 Patients</p>

“…The therapy with targeted agents in the Czech Republic outside of clinical trials is reimbursed only in comprehensive cancer centers, and the registry has been estimated to provide data on approximately 95% of all patients treated with targeted therapy for mCRC in these centers. 8 There are 17 comprehensive cancer centers and all have contributed to the database. The contribution to the patient-based database was mandatory for regorafenib reimbursed by public health insurance.…”

Characteristics and Absolute Survival of Metastatic Colorectal Cancer Patients Treated With Biologics: A Real-World Data Analysis From Three European Countries

“…The comparison of our findings to other studies using real-world data from Europe is hampered regarding studies using certain criteria to select patients, e.g., if they excluded patients with early disease progression ( 11 , 12 ) or focused on patients with metachronous metastases ( 13 ). A study from the UK based on medical records, which included unselected patients with advanced CRC ( N = 714) similar to our approach, confirmed our findings.…”

“…So far, available studies using real-world data such as administrative claims are often based on data from the United States (8)(9)(10). To our knowledge, real-world evidence based on routinely collected data on utilization of biologics in CRC patients from Europe is limited to two studies from the Czech Republic using data from a specific drug registry, one study from the Netherlands using data from a regional cancer registry, and one from Italy based on five regional cancer registries (11)(12)(13)(14). Large claims or medical record databases from Europe have thus not been used for this purpose so far.…”

Methylation-Based Therapies for Colorectal Cancer

“…Aderka et al [ 143 ] hypothesized that the discrepancies monitored between these two trials, CALGB80405 and FIRE-3, can be due to the trial-specific sequence of chemotherapy plus targeted therapy. However, a recent study of Buchler et al [ 144 ] showed no differences in OS between cohorts treated with first-line bevacizumab and second-line EGFRi (cetuximab or panitumumab) vs. the reverse sequence. Another difference between the data presented by the CALGB80405 and FIRE-3 groups was observed for CMS1 and MSI tumors.…”