QTWiST analysis to compare the benefit of maintenance Erlotinib versus pemetrexed patients with EGFR non mutated NSCLC

Abstract

Background:In an open label, Phase 3 randomised study, Pemetrexed maintenance after induction with 4-6 cycles of pemetrexed -Platinum therapy failed to prove its superiority over Erlotinib in patients with EGFR non mutated NSCLC. In this analysis we have assessed the benefit of erlotinib over Pemetrexed using quality adjusted time without symptom or toxicity analysis method. Methods: The overall survival in each arm was partitioned into 3 health states. TOX state (Time spent in grade 3 or above toxicity after randomization and before progression), TWiST state (Time spent after randomization before progression without grade 3 or above toxicity) and REL state (Time spent after progression). The mean QTWiST was calculated for each arm using utility coefficients of 0.65 for TOX, 0.71 for TWiST and 0.67 for REL states respectively. The difference in QTWiST and the 95% CI of difference were calculated using a nonparametric bootstrap. A p value of 0.05 was considered as significant. Results: The mean TOX duration was 2.216 days in Erlotinib arm versus 1.359 days in pemetrexed arm, p ¼ 0.572. The mean TWiST duration was 215.85days in Erlotinib arm versus 217.605 days in pemetrexed arm, p ¼ 0.945. The mean REL state duration was 198.620 days in Erlotinib arm versus 196.254 days in maintenance pemetrexed arm, p ¼ 0.932. There was no statistically significant difference between the two arms in mean TOX duration, mean TWiST duration and mean REL state duration. The mean QTWiST was 287.770 days in Erlotinib arm versus 286.873 days in Pemetrexed arm. The difference was of -0.897 days (95% CI -22.475 -20.681, p value 0.935). Conclusions: The mean QTWiST of Erlotinib arm was similar to maintenance Pemetrexed arm. Our results failed to prove the benefit of Erlotinib over Pemetrexed maintenance post induction with 4-6 cycles of pemetrexed -Platinum therapy in terms of quality adjusted time without toxicity.