Cost effectiveness of personalized therapy for first-line treatment of stage IV and recurrent incurable adenocarcinoma of the lung

Abstract

Purpose: Patients with epidermal growth factor receptor (EGFR) mutation-positive stage IV adenocarcinoma have improved survival with tyrosine kinase inhibitor (TKI) treatments, but the cost effectiveness of personalized first-line therapy using EGFR mutation testing is unknown.

Methods: We created a decision analytic model comparing the costs and effects of platinum combination chemotherapy with personalized therapy in which patients with EGFR mutation-positive tumors were treated with erlotinib. We used two testing strategies: testing only those with tissue available and performing a repeat biopsy if tissue was not available versus three nontargeted chemotherapy regimens (ie, carboplatin and paclitaxel; carboplatin and pemetrexed; and carboplatin, pemetrexed, and bevacizumab).

Results: Compared with a carboplatin plus paclitaxel regimen, targeted therapy based on testing available tissue yielded an incremental cost-effectiveness ratio (ICER) of $110,644 per quality-adjusted life year (QALY), and the rebiopsy strategy yielded an ICER of $122,219 per QALY. Probabilistic sensitivity analysis revealed substantial uncertainty around these point estimates. With a willingness to pay of $100,000 per QALY, the testing strategy was cost effective 58% of the time, and the rebiopsy strategy was cost effective 54% of the time. Personalized therapy with an EGFR TKI was more favorable when the nontargeted chemotherapy regimen was more expensive. Compared with carboplatin, pemetrexed, and bevacizumab, ICERs were $25,547 per QALY for the testing strategy and $44,036 per QALY for the rebiopsy strategy.

Conclusion: Although specific clinical circumstances should guide therapy, our cost-effectiveness analysis supports the strategy of testing for EGFR mutations in patients with stage IV or recurrent adenocarcinoma of the lung, rebiopsying patients if insufficient tissue is available for testing, and treating patients with EGFR mutations with erlotinib as first-line therapy.

Figure 1.

Cost-effectiveness frontier. Costs and effects of each of the nine potential treatment strategies are plotted. Strategies 4, 5, 7, and 8 lie inside of the cost-effectiveness frontier, because alternative strategies are preferred to them. QALY, quality-adjusted life year.

Figure A1.

Baseline decision tree reflecting three testing strategies. Each path contained possible adverse events, which are not shown here. EGFR, epidermal growth factor receptor.

Figure A2.

Probabilistic sensitivity analysis of carboplatin plus paclitaxel under the test strategy versus the same regimen under the base strategy. The ellipse represents the 95% CI, and it spans all four quadrants of the cost-effectiveness plane. QALY, quality-adjusted life year.

Figure A3.

Probabilistic sensitivity analysis of carboplatin plus paclitaxel under the rebiopsy strategy versus the same regimen under the test strategy. The ellipse represents the 95% CI, and it spans all four quadrants of the cost-effectiveness plane. QALY, quality-adjusted life year.

Figure A4.

Cost-effectiveness acceptability curve. On the basis of the probabilistic sensitivity analysis, all strategies are cost effective slightly more than 50% of the time over a wide range of cost-effectiveness thresholds. Bev, bevacizumab; Carb, carboplatin; Pac, paclitaxel; Pem, pemetrexed.