At the recent Chicago lung cancer meeting, the idea of maintenance therapy emerged as a hot topic that is experiencing ongoing changes in our treatment approaches over time. The controversies about this topic begin with the very terminology. Here are four proposed names for the same basic idea:

1) maintenance therapy, which implies that one of the initial treatments is being continued on a longitudinal basis

My kids are right in the middle of that time when they watch SpongeBob and see commercials for toys, cereals, and music, nearly every one is puncuated at the end with, "Daddy, can we get that? I want that." There comes a time in everyone's life, hopefully early on, when we learn that we won't actually find eternal bliss with every advertised item.

As a general rule, companies don't sit on great news with their drugs. Without any insider knowledge, this was my concern about why we hadn't heard anything about the results of three major lung cancer trials with the agent Zactima (vandetanib), which I had written a post about 8 months ago (see prior post about these trials with Zactima, an oral agent that inhibits both VEGF, a major mediator of angiogenesis, and the EGFR pathway).

Continuing on the introduction to the concept from a recent prior post, the issue of whether it’s important to see an improvement in progression-free survival (PFS) if there is no improvement in overall survival (OS) after additional therapy is going to be a central issue in lung cancer management, relevant in several key issues in coming years.

Well, it happened again that the first word came from the financial community (report here), as we learned today that a large trial testing the value of maintenance tarceva (erlotinib), the oral EGFR inhibitor, provides a significant improvement in progression-free survival (PFS). In the following slide, I show the design for two similar trials that test the value of tarceva after four cycles of first line treatment of advanced NSCLC.

I just recently wrote a post (here) that describes how I became convinced that under certain circumstances there could be a genuine value in determining whether a particular lung cancer patient has a tumor with an EGFR activating mutation.

Those who have followed my writings over time will know that I haven’t been inclined to adopt a reflexive strategy of ordering molecular testing without good evidence that having this information will improve outcomes. Testing tumors for EGFR mutations is advocated by a vocal minority of lung cancer experts in Boston and New York City, but this hasn’t been advocated by the broader lung cancer community yet, or adopted as routine clinical practice.

Though EGFR inhibitors like tarceva can produce some terrific and long-lasting results in many patients, they aren't toxicity-free. The "targeted therapies" we use just have a very different side effect profile from standard chemo, and the EGFR inhibitors are well known to have skin-related side effects as the leading problem, with loose stools/diarrhea as a less nearly ubiquitous second place issue.

The general approach to NSCLC is in transition right now, as the line between first and second line therapy are becoming increasingly blurred. A few years ago, the clear standard was that we usually stop first line chemo after four to six cycles, then follow a patient clinically and radiographically until they show evidence of progression, at which time we’d start second line treatment.

One of the central ideas in medical oncology is that if you have two or more anticancer treatments that are active, you test them together to determine whether it's safe and whether the combination works better than each individually. We've been doing this with chemotherapy combinations for decades, but it's only been in the last few years that we have had more than one targeted therapy in lung cancer with enough activity to move ahead with combination work.