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

PURPOSE: 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.

Impact of Delayed Addition of Anti-EGFR Monoclonal Antibodies on the Outcome of First-Line Therapy in Metastatic Colorectal Cancer Patients: a Retrospective Registry-Based Analysis.

BACKGROUND: The addition of monoclonal antibodies targeting the epidermal growth factor receptor (anti-EGFR Abs) to chemotherapy for metastatic colorectal carcinoma (mCRC) is commonly delayed in the real-world clinical practice, usually because of late RAS testing results. OBJECTIVE: To determine whether delayed addition of anti-EGFR mAbs up to the fourth cycle of backbone chemotherapy adversely affected outcomes of mCRC patients treated with first-line regimens. PATIENTS AND METHODS: Clinical data of patients with histologically verified, RAS wild-type mCRC treated with first-line systemic therapy regimens containing anti-EGFR mAbs were retrospectively analysed from a national database. Patients were divided into three groups according to the timing of anti-EGFR mAbs addition to the chemotherapy backbone. Cohort A (n = 401) included patients in whom anti-EGFR mAbs were added to chemotherapy from the first cycle, cohort B (n = 71) patients with anti-EGFR mAbs added to chemotherapy from the second cycle, and cohort C (n = 101) patients who had anti-EGFR mAbs added to chemotherapy from the third or fourth cycle. RESULTS: Three hundred and thirty-six (58.6%) patients received panitumumab and 237 (41.4%) patients received cetuximab. The median progression-free survival (PFS) of the whole cohort was 12.2 months (95% confidence interval [CI] 10.9-13.5), and the median overall survival (OS) was 33.5 months (95% CI 27.6-39.4). The median PFS and OS for patients treated with anti-EGFR mAbs added to chemotherapy were 12.9 (95% CI 11.5-14.3) and 30.6 months (95% CI 25.2-36.1) for cohort A, 9.7 (95% CI 9.1-10.3) and not reached for cohort B, compared to 11.5 (95% CI 9.8-13.2) and 37.9 months (95% CI 28.6-47.3) for cohort C, respectively. CONCLUSIONS: Delayed addition of anti-EGFR mAbs to first-line chemotherapy was not associated with inferior survival or response rates.

Bevacizumab with FOLFIRI or XELIRI in the First-line Therapy of Metastatic Colorectal Carcinoma: Results from Czech Observational Registry.

AIM: To retrospectively compare the efficacy of two irinotecan-based chemotherapy regimens combined with bevacizumab in first-line therapy of metastatic colorectal cancer (mCRC). PATIENTS AND METHODS: The data of 558 patients with mCRC treated with first-line bevacizumab plus irinotecan-containing regimen were obtained from the national CORECT registry that collects data of all patients with mCRC treated with targeted-agents. The treatment outcomes of patients treated with bevacizumab plus irinotecan, 5-fluorouracil and folinic acid (FOLFIRI) were compared to patients treated with bevacizumab plus irinotecan and capecitabine (XELIRI). RESULTS: Among 4,312 patients with CRC treated with bevacizumab, only 13% (558) received irinotecan-based chemotherapy. No significant differences were observed in terms of progression-free survival and overall survival between FOLFIRI and XELIRI groups. Moreover, the toxicity of both regimens was also comparable. CONCLUSION: This retrospective analysis confirms the comparable activity of FOLFIRI and XELIRI regimens when combined with bevacizumab.

Bevacizumab with 5-fluorouracil, leucovorin, and oxaliplatin versus bevacizumab with capecitabine and oxaliplatin for metastatic colorectal carcinoma: results of a large registry-based cohort analysis.

BACKGROUND: Data from the Czech national registry were analysed retrospectively to describe treatment outcomes for capecitabine and oxaliplatin (XELOX) regimen with bevacizumab versus 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX) regimen with bevacizumab in the first-line therapy for metastatic colorectal cancer (mCRC). METHODS: A national registry containing anonymised individual data on patients treated with targeted therapies was used as a data source. In total, 2,191 mCRC patients who received a first-line therapy with bevacizumab combined with either FOLFOX regimen (n = 1,218, 55.6%) or XELOX regimen (n = 973, 44.4%) were included in the present analysis. RESULTS: No statistically significant difference in survival was observed between the two groups, with median overall survival (OS) of 27.0 months (95% confidence interval [CI] 24.6-29.5 months) and 30.6 months (95% CI 27.8-33.4 months) for FOLFOX/bevacizumab and XELOX/bevacizumab, respectively (p = 0.281). Median progression-free survival (PFS) was 11.4 months (95% CI 10.7-12.1 months) for FOLFOX/bevacizumab and 11.5 months (95% CI 10.8-12.3 months) for XELOX/bevacizumab (p = 0.337). The number of metastatic sites was identified as the most significant predictor of PFS and, together with the presence/absence of metastatic disease at diagnosis, also for OS. CONCLUSIONS: According to this large registry-based analysis, XELOX and FOLFOX regimens have similar effectiveness for use in combination with bevacizumab in the first-line treatment of mCRC. Multiple metastatic sites and the presence of metastatic disease at diagnosis were the strongest negative predictors of OS regardless of backbone chemotherapy regimen.

Prognostic factors in patients with esophageal carcinoma treated with chemoradiation: single center experience.

BACKGROUND/AIMS: The trimodality therapy including chemotherapy, external beam radiation and surgery is widely accepted as the standard of care in patients with locoregional esophageal carcinoma. METHODOLOGY: We have performed a retrospective analysis of patients with locoregional esophageal carcinoma treated with chemoradiation. RESULTS: One-hundred and fifty-two consecutive patients with non-metastatic adenocarcinoma or squamous cell esophageal carcinoma treated with chemoradiation were included in the present analysis. The median survival of the whole group was 12 months. The estimated 3- and 5-year survival rates were 24% and 19%, respectively. On multivariate analysis, female sex, weight loss and serum albumin were independent negative predictors of survival. Among 140 patients who survived more than 3 months, weight loss, female sex and therapy with paclitaxel were negatively associated with prognosis, and among 109 patients surviving more than 6 months the dose of cisplatin and surgery were independent prognostic factors. Pathologic complete response was not predictive of prognosis. CONCLUSIONS: Long-term survival is obtained in only about 20% of patients with carcinoma of the esophagus treated with chemoradiation. Female sex, weight loss and low serum albumin are independent indicators of poor prognosis. Among treatment-related factors, higher dose of cisplatin and esophagectomy were independent predictors of better prognosis, while administration of paclitaxel was associated with poor prognosis.