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:

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.

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).

Immune-based approaches in lung cancer tend to generate significant buzz among patients and the general public, as well as in the media, but not as much optimism within the oncology world. Much of that is for good reason: while the concept of a minimally toxic, long-lasting anti-cancer approach like a vaccine is very appealing to all of us, oncologists have seen many hyped immune-based therapies deliver far less than their promise. This is for several reasons.

In contrast to the guidelines that exist for treating advanced lung cancer in the first-line setting for 4-6 cycles, there are really just practice patterns and good judgment to guide decisions of how long to treat in the second-line therapy. First, this is a relatively new question. As I previously mentioned when describing the history of treatment for advanced lung cancer, ten years ago there was plenty of debate about whether the benefits of treating NSCLC were sufficient to make this a standard of care.

The guidelines from the American Society for Clinical Oncology (ASCO) for NSCLC start the discussion on how long to continue first-line chemo as follows: "The optimal duration of chemotherapy remains a matter of debate." Just in case you thought it was only me saying that we don't know the exact answer for one issue or another, the evidence-based guidelines are filled with hedge comments like this.

We've come along way over the past decade. In the first half of the 1990s, the value of treating metastatic NSCLC was debated and not clear. A "meta-analysis" that pooled the results from 11 chemotherapy trials, 8 with cisplatin, and nearly 1200 patients demonstrated a modest but convincing improvement in survival compared to supportive care alone (article here). The figure summarizing the improvement by adding chemo is shown here:

In my last post, I described our evolving recognition in the lung cancer field that significant response as the threshold for clinical benefit is too high and that stable disease is likely a relative benefit as well. An important trial presented by Dr.