Prior bevacizumab and efficacy of later anti-epidermal growth factor receptor antibodies in metastatic colorectal cancer: results from a large international registry

The sequencing of biologic agents used in metastatic colorectal cancer can affect the outcomes. We analyzed a multicenter registry to address a question that could not be answered using current clinical trial data. We found that whether or not patients had received previous bevacizumab, the effect of epidermal growth factor receptor antibodies in later lines of therapy was maintained. Background: The FIRE-3 [5-fluorouracil, folinic acid, and irinotecan (FOLFIRI) plus cetuximab versus FOLFIRI plus bevacizumab in first line treatment colorectal cancer (CRC)] study reported that first-line FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab resulted in similar progression-free survival (PFS) but improved overall survival (OS). A potential explanation is that the initial biologic agent administered in metastatic CRC (mCRC) affects later line efficacy of the other treatments. We sought to test this hypothesis. Materials and Methods: We interrogated our mCRC registry (Treatment of Recurrent and Advanced Colorectal Cancer) regarding treatment and outcome data for RAS wild-type patients receiving epidermal growth factor receptor inhibitors (EGFRIs) in second and subsequent lines. Survival outcomes from the beginning of EGFRI use were determined as a function of previous bevacizumab use and the interval between ceasing bevacizumab and beginning EGFRI use. Results: Of 2061 patients, 222 eligible patients were identified, of whom 170 (77%) had received previous bevacizumab and 52 (23%) had not. PFS and OS from the start of EGFRIs did not differ by previous bevacizumab use (3.8 vs. 4.2 months; hazard ratio [HR], 1.12; P =.81; 9.0 vs. 9.2 months; HR, 1.19; P =.48, respectively) for the whole cohort or when analyzed by the primary tumor side (HR for left side, 1.07; P =.57; HR for right side, 1.2; P =.52). PFS was significantly shorter with right-sided primary tumors when the interval between bevacizumab and EGFRI use was 6 months (median, 2.2 vs. 6 months; HR, 2.23; P =.01) but not with left-sided tumors (median, 4.2 vs. 5.5 months; HR, 1.12; P =.26). Conclusion: Previous bevacizumab use had no effect on the activity of subsequent EGFRIs. The apparent effect of time between biologic agents in right-sided tumors might reflect patient selection

The management of colorectal cancer in Australia: heterogeneity of care and the need for increased data collection

© 2011 Dr. Suzanne KosmiderAustralia has one of the highest world-wide incidence rates of colorectal cancer, affecting one person in 20. It is the second most commonly diagnosed invasive malignancy. Each year, approximately 14,200 cases are diagnosed representing 13.1% of all incident cancer diagnoses. Of those diagnosed, about 50% will ultimately die from metastatic disease. After lung cancer, it is the second leading cause of cancer death in our country, resulting in around 80 deaths each week. Multiple factors impact on peoples’ outcomes, with stage at diagnosis being the most significant factor. Despite the commonness of this condition in our community, there are a number of areas where data are lacking, resulting in treatment uncertainty. These areas include the medical management (chemotherapy dosing, selection of appropriate candidates for adjuvant and metastatic therapy) and staging and surveillance strategies (optimal imaging modalities) for those diagnosed with this condition. The publications comprising this thesis examine these various aspects of colorectal cancer management in Australia. A recurrent finding arising from the research is the distinct heterogeneity of care, with no adopted standard. This emphasises the need for ongoing data collection in this area and proposed methods to address this issue are discussed in the later part of the thesis. The thesis comprises of four chapters, each focussing on a specific area of colorectal cancer management in Australia. A review of the current literature and discussion of the common themes precedes each set of associated publications. (Part Thesis Overview and Introduction only

Serious hepatic complications of selective internal radiation therapy with yttrium-90 microsphere radioembolization for unresectable liver tumors

Aim: Selective internal radiation therapy with yttrium-90 microsphere radioembolization has been used to treat unresectable liver tumors and its acute toxicity has been well described. Subacute and long-term hepatic complications related to radioembolization however may be underreported in the literature. This retrospective study describes the incidence and sequelae of serious hepatic complications in patients who underwent radioembolization for unresectable liver tumors. Methods: A retrospective review of clinical notes of patients who received radioembolization for unresectable liver tumors from 2001 to 2011 at two Australian institutions was performed to identify those who developed clinically significant hepatic complications. Relevant clinical data were obtained and analyzed to determine their incidence and sequelae. Results: A total of 205 patients were identified, of whom 10 (4.9%) developed serious hepatic complications with 7 (3.4%) attributable to radioembolization-induced liver disease. None had preexisting underlying liver disease or progressive hepatic metastases at the time of developing hepatic complication. The median time to the onset of hepatic complications was 3.5 months (range 1-67 months); six patients had a complete resolution eventually, including one patient who subsequently underwent hepatic metastasectomy safely. Three patients died as a result of fulminant hepatic failure. Conclusion: Selective internal radiation therapy with radioembolization was associated with serious hepatic complications with an incidence of 4.9% and a mortality rate of 1.5% in 205 patients from two Australian institutions. The risk of serious hepatic toxicity therefore needs to be discussed when counseling patients regarding this potential treatment option

Impact of Diabetes Status and Medication on Presentation, Treatment, and Outcome of Stage II Colon Cancer Patients

Diabetes is a risk factor for colorectal cancer and several reports suggest worse cancer-specific outcomes in diabetes patients. Recent studies in multiple tumour types indicate metformin may positively impact on cancer-specific and overall survival. A populationbased series of stage II colorectal cancer patients treated and followed from 2000 to 2013 were analysed for baseline characteristics, treatment, and outcomes. 1116 patients with stage II colon cancer were identified, 55.5% were male and median age was 70.9 years (range 20.5-101.2). The diabetes patients (21.6%, n = 241) were older than nondiabetes patients (median 74.0 versus 69.6, p = 0.0001). There was no impact of diabetes on cancer presentation or pathology. Diabetes patients were less likely to receive adjuvant treatment (13.7 versus 24.8%, p = 0.002) but were equally likely to complete treatment (69.7 versus 67.7%, p = 1.00). Diabetes did not significantly impact cancer recurrence (HR = 1.07, 95% CI 0.71-1.63) or overall survival (HR = 1.23, 95% CI 0.88-1.72), adjusted for age. Diabetes medication did not impact cancer recurrence or survival. Cancer presentation and outcomes in diabetes patients are comparable to those of nondiabetes patients in those with stage II colon cancer. The effect of metformin merits further evaluation in patients with colon cancer