Bevacizumab Data Gives Hope to Colorectal Cancer Patients with Liver Metastases

New data from several studies presented at the joint multidisciplinary meeting of ECCO 15 (European CanCer Organisation) and ESMO 34 (European Society for Medical Oncology) in Berlin, Germany, confirm unique benefits of bevacizumab (Avastin®, Roche, Basel, Switzerland), an antibody that specifically binds and blocks VEGF (vascular endothelial growth factor), and capecitabine (Xeloda®, Roche, Basel, Swizerland), a highly effective targeted oral chemotherapy offering patients a survival advantage when taken on its own or in combination with other anticancer drugs, in treatment of colon cancer.

Colorectal cancer is the second most common cause of death from cancer across all tumor types in Europe and is the third most commonly reported cancer in the world.

Bevacizumab in combination with chemotherapy led to shrinkage or disappearance (overall response rate) of liver metastases (disease that has spread to the liver) in 78% of patients with advanced colorectal cancer. As a result, one third (33%) of patients who were initially unable to undergo surgery were eligible to undergo a potentially lifesaving surgery. Complete surgical removal of the metastases was achieved in 56% of all bevacizumab-treated patients.

II BOXER study
The multicentre phase II BOXER study, a single arm phase II study, investigated the efficacy and safety of bevacizumab in combination with oral capecitabine and intravenous oxaliplatin (NO16968 XELOX trial, an open-label, randomised, phase III study of oral capecitabine in combination with intravenous oxaliplatin versus 5-fluorouracil/leucovorin (5-FU/LV) as adjuvant therapy for patients with stage III colon cancer who have undergone surgery) in patients considered unsuitable for upfront resection (surgical removal) of their liver metastases.

Response rates in this trial were measured by RECIST criteria. Secondary objectives of BOXER trial included complete resection rate, safety and feasibility of the regimen, PFS and overall survival.

“The data from BOXER shows that bevacizumab in combination with standard chemotherapy has the ability to shrink metastatic lesions which might allow surgical removal and therefore offer a potential for cure for patients with advanced disease,” explained Professor David Cunningham, Head of the Gastrointestinal Unit at the Royal Marsden Hospital, UK.

First BEAT
Data from the large, observational First BEAT phase IV trial assessing the safety and efficacy of bevacizumab in almost 2,000 previously untreated patients with mCRC in combination with a variety of standard chemotherapies, showed that bevacizumab -based treatment delivers the same benefits to all patients including those aged above 65 years who represent the majority of people with advanced colorectal cancer. This is an important finding as older patients are often under-represented in clinical trials. The study results showed that the time patients lived without their disease advancing (PFS) was similar across age groups – 10.8 months for those below 65 years, 11.2 months for those between 65 and 74 years and 10 months for those 75 years and older.

The most common chemotherapy regimens combined with bevacizumab in First BEAT were FOLFOX, XELOX, FOLFIRI (oxaliplatin, fluorouracil and irinotecan) and capecitabine. The primary endpoint of First BEAT was safety and secondary objectives were PFS and overall survival.

NO16968 (XELOXA) study
Patients taking capecitabine with oxaliplatin immediately after surgery live disease free for longer compared to those treated with commonly used chemotherapy regimen. New results for capecitabine in early colon cancer were also presented at the ECCO 15 - ESMO 34 meeting. The pivotal NO16968 (XELOXA) study, the largest-ever study of patients with stage III colon cancer, showed that the three year disease-free survival (DFS) for patients receiving XELOX was 70.9%, superior to the 5-FU/LV arm (66.5%) (HR=0.80 (95% CI: 0.69-0.93), p=0.0045). The DFS result obtained with XELOX is similar to that shown in trials evaluating the use of FOLFOX in patients with stage III colon cancer.

"We know that XELOX helps keep patients free from recurrence of their cancer longer,’’ said Dr Dan Haller, Professor of Medicine, University of Pennsylvania. "These results now confirm that patients have an additional option for the treatment of stage III colon cancer. In these potentially curable patients, XELOX offers the additional benefit of an oral medication, Xeloda."

"Colorectal cancer sadly claims more than 600,000 lives each year, despite the treatment advances made in the last decade” said William M. Burns, CEO of Roche’s Pharmaceuticals. “Today’s announcements about Avastin and Xeloda are therefore very welcome news for patients and their families as they offer more options for fighting this disease and hope that some patients may even have the potential to be cured” he added.

Images courtesy American Society of Clinical oncology (ASCO) and Roche Pharmaceuticals.