Lung cancer is the most common cancer worldwide with 1.2 million new cases diagnosed annually. The development of Avastin (bevacizumab) and Tarceva are promising to improve this situation as well as offering hope to other patients with diverse cancers (see Innovative Agents in Lung and Colorectal Cancer). Researchers conducting a phase I/II study now report that the combination of Avastin and Tarceva may be of benefit to patients with advanced non-small cell lung cancer (NSCLC) as well as with other solid tumors.

Lung cancer is the most common cancer worldwide with 1.2 million new cases diagnosed annually. The prognosis of patients is historically poor however targeted therapeutics such as Genentech/Roche's Avastin (bevacizumab) and Genentech/OSI Pharmaceuticals’ Tarceva, are promising to improve this situation as well as offering hope to other patients with diverse cancers (see Innovative Agents in Lung and Colorectal Cancer).

The development of growth factor inhibitors is a field that has attracted significant attention from the drug development sector. Despite disappointments surrounding AstraZeneca's Iressa (Gefitinib, ZD1839), a small molecule that specifically inhibits the tyrosine kinase activity of the epidermal growth factor receptor (EGFR) type 1, the development of Tarceva, which has recently been approved for the treatment of non-small cell lung cancer, has been more promising. This EGFR-1 tyrosine kinase inhibitor, like Avastin, can extend survival time by up to 40% compared to placebo when used as a second or third line monotherapy. In a recently reported pivotal study, patients receiving Tarceva had a median survival of 6.7 months compared to 4.7 months in patients who received placebo. This study led in 2004 to the FDA approving Tarceva for the treatment of patients with locally advanced or metastatic non-small cell lung cancer (press release).

Tumor vascularization is key to the development of solid tumors and hence the development of angiogenesis inhibitors has, like the focus on growth factor inhibitors, been a priority from the drug development community over the past decade and Avastin has been the most successful product of research efforts in this field to date. Although there are multiple opportunities for the development of anti-angiogenic molecules, the most advanced targets are the growth factors. One of the principal growth factors driving angiogenesis is VEGF and Avastin is a monoclonal antibody that binds to VEGF preventing the activation of its receptors. Particularly interim Phase III data has been recently reported by Roche demonstrating that Avastin in combination with a platinum based chemotherapy (paclitaxel and carboplatin) improves overall patient survival compared to chemotherapy alone (reported at the 2005 ASCO meeting; press release). This was the first time in years that a study has shown an increase in survival for people with non-small cell lung cancer in the first-line setting.

Given the remarkable survival data for both Avastin and Tarceva in non-small cell lung cancer, an otherwise difficult to treat cancer, the sales of these two agents is expected to be high. Current forecasts for US Tarceva sales in 2006 range from $300 million to $600 million and between 0.5 and $1 billion in by 2008. Peak sales of Avastin are expected to reach as high as $1.7 billion now that European approval has been granted.

Preclinical data has demonstrated a synergistic effect when Avastin and Tarceva are employed side by side. The JCO paper highlighted here reports a phase I/II study suggesting that the combination may be of benefit to patients with advanced non-small cell lung cancer as well as with other solid tumors. Out of 40 patients, 8 had partial responses under combination therapy while 26 had stable disease as their best response. The median overall survival for 34 patients treated in the phase II component of the trial was 12.6 months, with progression-free survival of 6.2 months. The overall survival data is similar to that reported in a recent Phase III trial (reported at the 2005 ASCO meeting; press release) evaluating the combination of Avastin and chemotherapy (12.5 months). This suggests that the combination of Avastin and Tarceva could represent an alternative to the combination of Avastin and chemotherapy and head to head studies comparing the efficacy and tolerability of these two strategies are eagerly awaited.

Entry date Thursday, June 02, 2005

J Clin Oncol. 2005 Apr 10;23(11):2544-55. Epub 2005 Mar 7