Reply to C.G. Azzoli et al and C. Chouaid et al.

Azzoli et al highlight the importance of molecular testing in non–small-cell lung cancer (NSCLC) and correctly identify that using multiplexed assays is a more cost-efficient method than testing for targets sequentially as used by the Markov model proposed by Djalalov et al. The Lung Cancer Mutation Consortium has recently reported that actionable driver mutations can be found in 64% of lung adenocarcinomas and that the median survival is now 3.5 years in those patients harboring an oncogenic driver targeted by genotype-directed therapy. Azzoli et al indicate that great science is an investment in the future, and we certainly agree with this sentiment, but this has to be balanced with the real-world economic realities of today. The hope that future competition in the marketplace and limits on exclusive production will ultimately bring down the price of drugs over time is flawed. Normal market economics do not apply when it comes to the pricing of cancer drugs. Azzoli et al have suggested that economies of scale will eventually decrease drug costs over time, but this has not occurred in the era of targeted oncolytics. The cost of imatinib is an excellent example with the price increasing from $25,000 per year when it received approval in 2001 to $92,000 per year in 2014. The reasons for this price escalation over the last decade are unclear and cannot be explained by wanting to recoup research and development costs and generating a reasonable return on investment given that those elements were factored in to the 2001 price. The effect that medical insurance has on the value equation is termed moral hazard, and patients have until recently been insulated from feeling the effects of rapidly escalating drug prices so that the price elasticity of demand is difficult to measure. With copayments and deductibles expected to continue increasing, consumer price sensitivity is expected to become more commonplace. Patients have indicated that personal responsibility for cost does increase sensitivity to the value of treatments. Chouaid et al state that limited or no cost-effectiveness analysis has been performed in recent years for NSCLC given that many of today’s treatment strategies commonly exceed the acceptable incremental costeffectiveness ratio threshold of $150,000. The next-generation ALK inhibitor ceritinib (LDK378) has been priced at $13,500 per month, which represents a 50% increase over the current price of the first generation ALK inhibitor crizotinib at $9,600 per month. This drug has demonstrated impressive activity in patients resistant to or progressing on crizotinib, but with no head-to-head comparisons, it is difficult to determine whether it is 50% more effective. With multiple other ALK inhibitors on the horizon, will we continue to see price escalation that will exclude only the very rich from benefitting? We and others have repeatedly called for a value-based pricing system. In January 2014, the American Society of Clinical Oncology organized a meeting entitled “Optimizing High-Value Cancer Care: Addressing the Cost of Drugs and Novel Technologies. ” The goal of this meeting was to open a dialogue among key stakeholders to enhance value as defined by the optimal clinical benefit per unit cost. The American Society of Clinical Oncology Value in Cancer Care Task Force is currently in the process of developing an algorithm to determine the relative value of cancer drugs. The first therapies being evaluated for cost effectiveness include those for advanced NSCLC, prostate cancer, and multiple myeloma. This much-needed approach will outline the clinical benefit as defined by overall or progression-free survival in addition to the qualityof-life improvement, the toxicity profile, and the costs associated with drug administration. Expert oncologists can and should play an integral role in determining value to protect both their patients and society. Patients with lung cancer outside the United States are already being deprived of access to first-generation ALK inhibitors like crizotinib as regulatory bodies, including the National Institute for Health and Care Excellence, have determined that they are too expensive when compared with commonly acceptable thresholds of cost effectiveness. Chronic myeloid leukemia experts have called for a price reduction in the recently approved drugs bosutinib and ponatinib, which each cost more than $100,000 per year. Price reductions in ziv-afilbercept were achieved partly as a result of colorectal oncologists advocating on behalf of their patients. We agree with Chouaid et al that cost-effectiveness analysis should be used to form policy around national health care plans, recognizing that each country will have different thresholds and that oncologists can play a key role.