ERLOTINIB, AFATINIB, AND CISPLATIN/PEMETREXED FOR FIRST-LINE TREATMENT OF ADVANCED EGFR-MUTATION POSITIVE NON-SMALL CELL LUNG CANCER: VALUE-OF-INFORMATION ANALYSIS
Method: We used data from two randomized clinical trials: 1)EURTAC (median age 62 years), comparing erlotinib to cisplatin plus carboplatin or gemcitabine, and 2)LUX-LUNG 3 (median age 65 years), comparing afatinib to cisplatin plus pemetrexed, for first-line EGFR-positive stage IIIB/IV NSCLC treatment. Survival probabilities of EURTAC were corrected for presence of participants with ECOG performance score >1. We developed a Markov model to simulate transition through progression-free survival (PFS), progression (overall survival [OS]-PFS), and death (1-OS) under erlotinib, afatinib, and cisplatin/pemetrexed, using a societal perspective and lifetime horizon. Survival and side-effect probabilities, obtained from the trials, costs (3% annual discounting), and utilities were modeled as distributions for probabilistic sensitivity analysis. Costs and quality-adjusted life years (QALY) were used to calculate incremental cost-effectiveness ratios (ICER). We constructed acceptability curves by plotting the proportion of simulations a treatment had the highest net benefit (NB=effectivenesness*willingness-to-pay[WTP]Cost) over a range of WTP thresholds. We calculated EVPI to estimate the expected benefit of further research to decrease decision uncertainty. We also identified parameters responsible for most of the decision uncertainty.
Result: In the base case, using societal WTP threshold of $100,000/QALY, erlotinib was cost-effective compared with afatinib, with a mean ICER of $61,809/QALY. The acceptability curve showed that erlotinib was the preferred treatment at WTP of $100,000/QALY. Uncertainty regarding decision of erlotinib versus afatinib was highest at WTP of $50,000-$70,000/QALY, and afatinib was preferred at WTP<$30,000/QALY. Population EVPI analysis showed that the maximum acceptable cost of reducing decision uncertainty is $46.5 million, assuming an effective lifetime for current treatments of 10 years at 3% discount annually. The following parameters were responsible for most of the decision uncertainty: monthly cost of erlotinib, monthly cost of afatinib, and the probability and cost of rash together for afatinib.
Conclusion: Erlotinib is the preferred treatment based on its ICER, compared with afatinib. At WTP of $60,000/QALY, further research to determine the optimal treatment is justified, given a trial of 230 participants, at $200,000/trial participant. However, further research is not justified at WTP of $100,000/QALY.