Iressa was approved by the US FDA in May of 2003 as a third-line therapy, and for the next 18 months it was the only EGFR inhibitor on the market.

I haven’t really covered the history or issues of directly comparing the two oral inhibitors of the epidermal growth factor receptor, or EGFR, which are Iressa (gefitinib) and Tarceva (erlotinib). This is really because over the last few years, gefitinib has had disappointing results in some important trials and is no longer readily used or available, while the remarkably similar drug Tarceva has been approved by the US FDA and is a standard treatment for patients with advanced NSCLC that has previously been treated with chemotherapy.

Although EGFR tyrosine kinase inhibitors and chemotherapy agents have been tested in previously treated patients with advanced NSCLC, and tarceva, alimta, and taxotere are all approved by the US FDA in this setting, we haven't had studies directly comparing chemo to targeted therapy. However, we're starting to get the first glimpses of information, including a randomized Phase III trial out of Japan that gave previously treated advanced NSCLC patients either iressa or taxotere.

Last week, Genentech had a press release in which they disclosed some potentially important information about a large randomized trial being done in Europe with Avastin. This study, known as the AVAIL trial, enrolled just over a thousand first-line patients with advanced NSCLC to receive their most common standard chemotherapy, cisplatin and gemcitabine, alone or in combination with Avastin at either of two dose levels, 7.5 mg/m2 and 15 mg/m2. The basic design is as shown in this figure:

When is surgery necessary or just particularly helpful for bone metastases? There are situations in which invasive approaches may be appropriate for the long bones (of the arms and legs). First, surgery can be helpful for persistent or increasing pain despite completing palliative radiation therapy.

We've established that bone metastases are common, and now we'll talk about approaches to manage pain that often accompanies them. As I mentioned previously, sometimes a metastases occurs in a weight-bearing bone, in which case we often recommend a prophylactic surgical procedure to stabilize the bone at risk for fracture. Radiation can also reduce the risk for fracture and improve pain.

While lobectomy or pneumonectomy may be the surgical treatment of choice for most NSCLC tumors in younger, fit patients, a limited resection may be an ideal choice in certain settings. In my previous post I discussed the data supporting a limited resection in older patients, who are likely to have competing health risks that may make it less critical to pursue the most aggressive surgical strategy. Another situation in which a sub-lobar resection may be particularly appealing is when the tumor is quite small and/or has characteristics suggestive of an indolent natural history.

While the prevailing standard of care for resectable lung cancer is a lobectomy or pneumonectomy, we want the surgery to be as appropriate as possible for patients. That means not short-changing patients by doing a lesser surgery than they need to do as well as possible with the cancer, but also not overtreating patients with a more aggressive surgery than they need. There are two main variables that potentially alter the equation and may make a sublobar resection a more appropriate consideration.

Surgery is the standard treatment for early stage lung cancer, sometimes also including other types of threrapy in addition. There are many types of lung cancer surgery, and there is still active debate about whether a pneumonectomy or lobectomy should be the preferred surgery for lung cancer, or whether a sub-lobar resection, either a segmentectomy or a wedge resection, is appropriate for certain patients. We need to start with some definitions.

As I mentioned in prior posts on the topic of second-line therapy, taxotere was the first treatment approved for second-line treatment of NSCLC. Back in 2000, first-line chemo with platinum-based doublets was becoming increasingly established as demonstrating a consistent survival benefit of several months for previously untreated patients with advanced NSCLC, and then a couple of trials came out that demonstrated a modest survival benefit that for second-line taxotere, compared to either supportive care alone or compared to alternative chemotherapy (navelbine or ifosfamide).