Over the past couple of years a few large trials have emerged that have shown some value in switching patients to a new chemotherapy after, for instance, four cycles of first line chemo for advanced NSCLC, vs. an otherwise very reasonable alternative of stopping treatment in non-progressing patients and following them off of treatment, until progression. To be more specific, the two key trials, one by Fidias and published recently in the Journal of Clinical Oncology, and the other, termed "JMEN" by Lilly, presented at ASCO 2008, looked at Taxotere (docetaxel) and Alimta (pemetrexed), respectively. Both found a highly significant improvement in progression-free survival, and a borderline but not quite significant improvement in overall survival, favoring "maintenance"/early second line therapy. More mature survival data for the Alimta trial are slated to be presented at ASCO 2009 and could reach statistical significance. The absolute survival difference in each of these trials is about 2.5 months in both of these trials. On top of these results, Genentech has announced that their trials of maintenance tarceva (erlotinib), termed ATLAS (chemo/avastin (bevacizumab) followed by avastin/tarceva vs. avastin/placebo maintenance) and SATURN (chemo followed by tarceva vs. placebo maintenance after 4 cycles of chemo) are both positive for progression-free survival as described in press releases, but with no discussion of overall survival thus far. The reports and actual data for these trials are scheduled for release at ASCO, and Genentech is showing signs that it is optimistic enough to be gearing up for an approval and launch of tarceva in the maintenance setting.

Thus far, though, uptake of the concept of immediate transition to maintenance/early second line therapy by experts and the general oncology community has been...muted. I personally am impressed that the results are arguably clinically significant, regardless of whether they're statistically significant (for overall survival, at least). However, it's fair to say that many and perhaps most experts aren't rushing to change their practice. And this is all against a backdrop of continuing first line treatments (avastin, erbitux (cetuximab), sometimes alimta, depending on the trial) as an ongoing therapy until progression. In short, we're seeing that idea of a break from treatment between first line and second line encroached upon from both sides: first line is extending out later, and second line is moving earlier. So my questions are these: 1) Do you (or the person you’re discussing treatment options with) value that break, so the level of evidence favoring a transition from first to second line needs to be very compelling? Or do you feel "vulnerable" and somewhat anxious being off of treatment, potentially “letting down your guard”? 2) Is the concept of maintenance more attractive for an oral therapy like tarceva than an IV chemo? I suspect that if the final results of the ATLAS and SATURN trials look favorable enough, Genentech and OSI likely to market the concept of oral therapy as being uniquely appealing as maintenance therapy. What do you think? There’s a poll with quick choice for the first question in the right column, but you can provide actual comments below.