Here's a summary of some early phase 2 results for Avastin. How can we be trading at $.40 while Avastin probably provides $12 bil in market cap to Genetech (with all the side effects)?
Bevacizumab has been studied in Phase II and III trials in over 1900 patients with meta-static colorectal cancer ( Table 1 ).[15,21-33] Two multicenter Phase III trials provided the bulk of efficacy and safety evidence leading to the approval of labeling as a first-line agent for meta-static colorectal cancer. The first of these trials randomized 925 previously untreated patients to therapy with (1) the Saltz regimen, (2) the Saltz regimen plus bevacizumab, or (3) fluorouracil, leucovorin, and bevacizumab.[21] The third group was later withdrawn from the study when new evidence demonstrated survival superiority for the Saltz regimen over the fluorouracil-leucovorin combination. The Saltz regimen plus bevacizumab had significant advantages compared with the Saltz regimen alone in overall survival time (20.3 versus 15.6 months [ p = 0.00003]), progression-free survival time (10.6 versus 6.24 months [ p < 0.00001]), overall response rate (45% versus 35% [ p = 0.0029]), and duration of response (10.4 versus 7.1 months [ p = 0.0014]).[21] Grade 3 and 4 toxicities were similar between the groups. However, grade 3 hypertension was significantly higher in the bevacizumab group (10.9% versus 2.3%).
Breast Cancer
Angiogenesis is an important step in the proliferation of breast cancer cells and is thought to precede invasive disease.[14] Immunohistochemistry staining has found high levels of VEGF in ductal carcinoma in situ cells, further rationalizing the investigation of bevacizumab for breast cancer. Two Phase III trials and three Phase II trials are seeking to identify bevacizumab's exact role in various combinations with capecitabine, paclitaxel, and vinorelbine and as monotherapy ( Table 2 ).[14,27,35-41] The only completed Phase III trial compared capecitabine monotherapy with capecitabine plus bevacizumab in 462 patients with metastatic breast cancer.[35,36] Inclusion criteria included prior treatment with an anthracycline and a taxane agent. No significant difference was found for time to disease progression (4.17 months for the control group versus 4.86 months for the bevacizumab group [hazard ratio, 0.98]). However, the overall response rate favored bevacizumab (19.8% versus 9.1% [ p = 0.001]). Bevacizumab was associated with hypertension, proteinuria, and minor mucosal bleeding. Evaluation of selected tumor samples showed that overexpression of VEGF RNA was not associated with response rate in the capecitabine-bevacizumab group.[36]
Non-Small-Cell Lung Cancer
Two Phase II trials of bevacizumab for stage IIIb and IV non-small-cell lung cancer are ongoing ( Table 3 ).[32,33,42-45] In these studies, bevacizumab is being combined with either carboplatin-paclitaxel or erlotinib in various dosage regimens. As a result of fatal hemoptysis in four patients receiving carboplatin-paclitaxel-bevacizumab, future clinical trials are likely to exclude patients with a history of hemoptysis.[32,33,42,43] The Phase II trial ( n = 34) with erlotinib demonstrated a partial response in 20% of patients and stable disease in 65%.[44] The median overall survival time was 12.6 months. A Phase III trial now under way is comparing the combination of carboplatin, paclitaxel, and bevacizumab with carboplatin plus paclitaxel. Patients with squamous-cell carcinoma are excluded, since this subset was associated with hemoptysis in the Phase II trial.[42]
Phase III data must be available before bevacizumab can be recommended as part of a standard treatment regimen for non-small-cell lung cancer.
AI
