One nagging question that people often ask about, or at least worry about, is whether they are compromising their ability to benefit from an EGFR tyrosine kinase inhibitor (TKI) like Tarceva (erlotinib) or Iressa (gefitinib) if they need to cut down on the dose because of problems with side effects. Anecdotally, I think just about every clinical oncologist believes that is absolutely not the case, based on the fact that many of our patients who have very dramatic and prolonged responses to EGFR inhibitors have also required one or more dose reductions and continue to do very well on a lower dose than the starting dose of Tarceva at 150 mg/day or Iressa at 250 mg/day. We also know from lab-based work that cancer cells with an EGFR mutation are about ten times as sensitive to the effects of EGFR TKIs than cancer cells without an EGFR mutation. This suggests that patients who have an NSCLC tumor with an EGFR mutation may require a lower than standard dose to still receive the benefits. At this year's ASCO meeting, Inoue and colleagues will present a retrospective analysis of outcomes based on dose for patients on their study of standard chemo vs. Iressa for patients with an EGFR mutation detected before starting first line therapy. (click on image to enlarge)

The retrospective analysis compares the results of 52 (46%) of patients who continued at full dose Iressa with the 62 (54% (!!)) who had a dose-reduction of Iressa, generally switching to once every two day treatment (because there are no lower dose tablets of gefitinib than 250 mg). The analysis showed no significant difference at all in outcomes, and even a numerically longer median progression-free survival of 351 days vs. 301 days, and median overall survival of 928 days vs. 852 days, for the lower dose vs. full dose recipients, respectively. This doesn't mean that lower dosing is a superior strategy (these are not close to statistically significant differences, and the groups aren't huge), but it should allay anyone's fears that the people who need to reduce dose of their EGFR inhibitor due to challenging side effects are compromising their treatment -- at least for patients who have tumors with an EGFR mutation.