![]() |
|||||||
|
You are here: Home: LCU 4 | 2006 : Vincent A Miller, MD
Select Excerpts from the Interview Track 2 ![]()
ASCO 2006 was important in terms of reporting some prospective trials of EGFR TKIs in patients known to have EGFR mutations. The lowest response rate in prospectively identified patients with mutations was about 65 percent, and it went up to about 85 or 90 percent (Miller 2006; Asahina 2006; Paz-Ares 2006; Sutani 2006; Sunaga 2006). So a patient has about a 75 or 80 percent chance of having a response if he or she has an EGFR mutation. That is pretty good compared to what we had two or three years ago and even compared to what we have in other commonly studied diseases that are driven by diagnostic testing. In our trial for patients with bronchoalveolar cancer — presented at ASCO 2006 — we had some patients with an EGFR mutation and a high EGFR copy number. Their response rate was 90 percent and their median survival was about three years with erlotinib. The response rate for patients without an EGFR mutation and with an EGFR copy number lower than four was four percent, and their median survival was only 15 months (Miller 2006). Those are pretty powerful predictors for a difference in clinical outcome with two tests. Track 8 ![]()
We saw nearly a 2.5-fold difference in median survival: 10 months for the control group, which was not significantly different from the survival for the whole study group, and 22.5 months for the group that received erlotinib with chemotherapy (Herbst 2005; [2.1]). Even in the most ambitious Phase II study from a single institution, I don’t believe we have ever seen a nearly two-year median survival in untreated patients with metastatic lung cancer. Given those data and having had a good experience with that regimen for my patients, I believe this is clearly an effective treatment for the majority of these individuals. They are not cured, and we don’t want to lose sight of the fact that we have a tremendous amount of work to do, but it is a palpable step forward in their therapy. ![]()
When you use erlotinib in that type of population, with a high frequency of EGFR mutations, you tend to induce apoptosis in the tumor cells. Therefore, you may not have an inhibitory or negative interaction between the chemotherapy and erlotinib. This has been demonstrated in cell lines.
Track 9 ![]()
Should erlotinib be continued or stopped? There is a raging debate on this with trastuzumab in breast cancer. Our data were fairly provocative that it may be beneficial to continue erlotinib. The rate of progression appeared greater among patients off erlotinib than among those on erlotinib (Riely 2006). We evaluated patients who either had a known EGFR mutation or had been on erlotinib or gefitinib for at least six months (ie, surrogates for benefit from the drug) and who then experienced documented progression. We obtained a CAT scan and a PET scan. We stopped the erlotinib, and we obtained the same scans three weeks later (Riely 2006). Then we restarted the erlotinib and repeated the CAT scan and PET scan three weeks later. Hence we had paired data at baseline, off erlotinib and back on erlotinib. We also had careful correlation of clinical symptoms (Riely 2006). We were impressed by the worsening symptomatology in that relatively short time period. Seven out of 10 patients felt worse when they had stopped receiving erlotinib, and then when they resumed the erlotinib, seven out of 10 patients either stabilized or felt better. Also, a suggestion was observed on the CAT and PET scans, particularly the PET scan, that some of the lesions flared and then quieted down when patients went back on the TKI (Riely 2006). Track 10 ![]()
We want to see if erlotinib alone looks as good as carboplatin/paclitaxel in the never-smoking population from the TRIBUTE trial. Will these patients have a 10-month median survival? We also want to see if the other group (chemotherapy with erlotinib) maintains the 23-month median survival that we saw for the never smokers in the TRIBUTE trial. Every patient on the trial must have adequate tissue for EGFR sequencing. We want to accrue enough patients with EGFR mutations to observe whether there’s a differential benefit between patients with an EGFR mutation and the oligosmokers at large. Maybe chemotherapy with erlotinib is better for the oligosmokers at large, but erlotinib alone looks as good as the combination for the patients with mutations.
|
|
![]() |
Terms of Use and General Disclaimer Copyright © 2006 Research To Practice. All Rights Reserved. |
![]() |