The impact of dose intensity on the efficacy of gemcitabine plus carboplatin (GC) therapy for recurrent platinum-sensitive ovarian cancer (PSOC): A retrospective analysis of AGO-OVAR 2.5.

Abstract

5088 Background: The gemcitabine plus carboplatin combination (GC) is known to provide a clinical advantage compared to single-agent C for patients (pts) with recurrent PSOC. Dose reductions and delays for toxicity are common during standard GC therapy. To evaluate the potential impact of G and C dose adjustments on clinical outcomes in pts with PSOC, we retrospectively analyzed dose intensity (DI) data from the phase III trial AGO-OVAR 2.5. Methods: Data analyses were performed for 175 GC-treated pts. G and C weekly DIs were calculated as the mean dose of drug received divided by the planned weekly dose for each pt through each cycle of treatment. Progression-free survival (PFS) and response rate (RR) were compared across G DI groups for pts who received 6 cycles using the log-rank test and Fisher’s exact test, respectively To reduce the bias of time dependence, we examined subsequent PFS after cycle 2 stratified by G DI within the first 2 cycles (in pts who received >2 cycles). Results: A total of 99 pts (56.6%) completed 6 cycles. The mean weekly G DI ranged from 89.5% at cycle 1 to 73.0% at cycle 6; the mean weekly C DI ranged from 99.5% at cycle 1 to 91.5% at cycle 6. Results for pts receiving either 6 cycles or >2 cycles are shown in the table. There were no significant differences across G DI groups for either PFS (P=0.199) or RR (P=0.537) for pts receiving 6 cycles or for subsequent PFS (P=0.249) when pts were grouped by G DI within the first 2 cycles. Comparisons of G and C DI based on the numbers of cycles completed (up to 8) also showed no significant differences in PFS or RR. Conclusions: Differences in DI of both G and C for pts receiving from 2 to 8 cycles of standard GC chemotherapy had no impact on either PFS or RR in the AGO-OVAR 2.5 trial. Protocol-specified dose adjustments do not appear to impact the efficacy of GC therapy for pts with PSOC. Patients receiving 6 cycles (n=99) Patients receiving >2 cycles (n=158) Mean DI of G by quartile N RR P Median PFS (months) P N Median PFS (months) P DI <25th percentile 25 64% 0.537 11.5 0.199 39 9.1 0.249 25th percentile ≤ DI < median 24 50% 8.9 39 8.4 Median ≤ DI <75th percentile 25 64% 10.0 40 6.4 DI ≥75th percentile 25 48% 7.6 40 7.7