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#2529 Prospective Analysis of Association Between in Vitro Extreme Drug Resistance Assay Results and Clinical Outcome for Ovarian Cancer Patients.
JP Fruehauf, RS Mehta, R Parker, R Burger, A Manetta; Oncotech, Inc., Irvine, CA; UC Irvine Medical Center, Orange, CA
We set out to prospectively determine if in vitro Extreme Drug Resistance Assay (EDRA) results could predict clinical outcomes for ovarian cancer patients treated with single agent paclitaxel (T), platinum (P), or a combination of TP or cyclophosphamide and P.
EDRA’s were performed on specimens from 450 patients. An interim analysis was performed for 31 of these patients where clinical outcomes were initially obtained.
EDRA results for the single agents or drug combinations that patients received as first line therapy fell into three categories: low drug resistance (LDR); percent cell inhibition [PCI]median), intermediate drug resistance (IDR; PCI=median to 1SD below the median), or extreme drug resistance (EDR; PCI 1SD below the median).
Clinical outcomes for the EDR (n=8) group were compared with the IDR/LDR (n=23) group. Physicians were blinded to ER assay results until after disease progression.
Median progression-free survival (PFS) was 4 mos for the EDR cohort, compared to 24 mos for the IDR/LDR cohort (Gehans Wilcoxon test, 2-tailed p=.006).
After adjusting for variables significant in univariate analysis, in vitro response retained significance as an independent predictor of PFS (p=.003, RR 4.3+/-2) and OS (p=.003, RR 5.6+/-1.7, Cox proportional hazard model).
For the subset of 12 suboptimally debulked cases, PFS at 15 mos favored the IDR/LDR group (n=6) over the EDR group (n=6)(Fisher’s exact test, p=.060). EDR patients also had a poorer OS at 24 mos (compared to the IDR/LDR group (p=0.152).
In conclusion, this interim analysis of our prospective study suggests that patients treated with agents that their tumors are resistant to in vitro have poorer outcomes. We are continuing to collect additional follow-up information for the entire cohort accrued to this study.
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