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3G-4
ERLOTINIB, AFATINIB, AND CISPLATIN/PEMETREXED FOR FIRST-LINE TREATMENT OF ADVANCED EGFR-MUTATION POSITIVE NON-SMALL CELL LUNG CANCER: VALUE-OF-INFORMATION ANALYSIS

**Purpose:**The optimal choice among erlotinib, afatinib, or cisplatin plus pemetrexed for first-line treatment of EGFR-positive stage IIIB/IV non-small cell lung cancer (NSCLC) in the United States is unknown. We evaluate the cost-effectiveness and expected value of perfect information (EVPI) of the three treatment strategies.

**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.