Update on Advanced Colorectal Cancer桝SCO 2005
Date: May 13-17, 2005
Location: Orlando, Florida
Author: Steven J. Cohen, MD and Neal J. Meropol, MD
Fox Chase Cancer Center
Colorectal cancer remai a serious health problem in the United States as the second leading cause of cancer death. De ite advances in the treatment of both early stage and advanced disease, nearly 40% of all patients diagnosed will die of their disease.
Over the past few years, the introduction of new systemic therapies has significantly improved median survival for patients with metastatic colorectal cancer from a roximately one year to nearly two years. At the 2005 American Society of Clinical Oncology (ASCO) meeting, key findings from advanced disease studies were presented. Several presentatio clarified optimal use of available therapies and introduced novel therapeutics. Highlights of these recent developments are summarized below.
Avastin?
Avastin (bevacizumab) improves survival when added to frontline IFL. <1>However, at ASCO 2004, Chen and colleagues presented results of a compa ionate use study of Avastin with 5-FU in heavily pretreated patients that resulted in only a 1% re o e rate. <2>Thus, the benefit of Avastin in refractory metastatic disease was unclear. At ASCO 2005, data were presented regarding the use of Avastin in second/third line therapy in combination with either FOLFOX or Erbitux?(cetuximab). Giantonio and colleagues presented results of ECOG 3200. This was a 3-arm phase III study of 822 patients with progre ive metastatic colorectal cancer after 5-FU and Camptosar?(irinotecan) who had not received prior Eloxatin?(oxiliplatin) or Avastin. <3> The primary endpoint was OS. Patients were randomized to receive FOLFOX, Avastin (10 mg/kg), or the combination. Patients treated with FOLFOX Avastin had an a roximately 2 month improvement in PFS and OS and improved re o e rate compared to FOLFOX monotherapy (Table 1). Re o e rates were improved by a roximately 10% with the addition of Avastin. Avastin monotherapy was inferior to both other arms. It is important to note that ECOG 3200 excluded patients who had received prior Avastin. Thus, it does not addre the second-line use of Avastin after failure of an Avastin-containing regimen. Rather, it serves to validate the notion that Avastin contributes additional benefit to FOLFOX.
Table 1: Results of ECOG 3200
FOLFOX Avastin (A)
FOLFOX (B)
Avastin (C)
p-value (A vs. B)
n
289
290
243
N/A
Re o e Rate (%)
21.8
9.2
3
<0.0001
PFS (m)
7.2
4.8
2.7
<0.0001
OS (m)
12.9
10.8
10.2
0.0018
Saltz et al. presented results of the 揃OND-2?study, which randomized patients to the arms of the original study (Erbitux vs. Erbitux/Camptosar) with Avastin added to both arms. <4>Eligibility include