Trends in Prices of Drugs Used to Treat Metastatic Non–Small Cell Lung Cancer in the US From 2015 to 2020

IMPORTANCE Oncology drug prices are a determinant of health disparities in the US and worldwide. Several new therapeutic agents for non–small cell lung cancer (NSCLC) have become available on the US market over the past decade. Although increased competition typically produces lower prices, competition among brand-name oncology drugs has not resulted in lower prices. OBJECTIVE To assess price changes in class-specific brand-name medications used to treat metastatic NSCLC in the US from 2015 to 2020. DESIGN, SETTING, AND PARTICIPANTS This cross-sectional study, conducted from August 13, 2015, to August 13, 2020, used data from the Micromedex Red Book and Medi-Span Price Rx databases. The study sample was limited to 17 brand-name medications used to treat metastatic NSCLC that were available for purchase before January 1, 2019. MAIN OUTCOMES AND MEASURES The main outcomes were trends over time in average wholesale prices and wholesale acquisition cost unit prices and the correlation in price among the multiple brand-name medications within each therapeutic class (immune checkpoint inhibitors, epidermal growth factor receptor inhibitors, anaplastic lymphoma kinase inhibitors, ROS1 inhibitors, BRAF inhibitors, and MEK inhibitors), measured using the Pearson correlation coefficient. The compounded annual growth rates of different medication costs were compared with the annual inflation rate and the consumer price index for prescription drugs. RESULTS For all drug classes, the Pearson correlation coefficient approached 1.0, indicating an increase in drug list prices despite within-class drug competition. The median Pearson correlation coefficient values were 0.964 (range, 0.951-0.994) for immune checkpoint inhibitors, 0.898 (range, 0.665-0.950) for epidermal growth factor receptor inhibitors, 0.999 (range, 0.982-0.999)


Introduction
Several new anticancer agents for treating metastatic non-small cell lung cancer (NSCLC) have been introduced to the US market. In capitalistic systems, increased competition is expected to lower prices; however, this has not been the case with competition among brand-name drugs within the same class in oncology. 1 Breakthroughs in immunology and genomics have led to the availability of multiple immunotherapy and small-molecule inhibitor drugs, often targeting the same pathway for the treatment of NSCLC. Despite this increased availability, little is known about within-class competition and its effects on the prices of these anticancer agents. Because numerous new drugs have been approved for the treatment of NSCLC in recent years, we sought to specifically study the price competition among drugs used to treat this cancer subtype. We evaluated the pattern of price changes for multiple brand-name medications used for treatment of metastatic NSCLC that were contemporaneous in the US market from 2015 to 2020.

Methods
We conducted a cross-sectional study of average wholesale prices (AWPs) for oral agents and wholesale acquisition cost (WAC) for intravenous agents for treatment of NSCLC in the US from August 13, 2015, to August 13, 2020 (Figure 1). The data were obtained from the Micromedex Red Book and Medi-Span Price Rx databases. The study sample was limited to brand-name medications  used for treating metastatic NSCLC that were available for purchase before January 1, 2019, to better characterize the pricing trends of the drugs that have been in the market for more than 1 year. When conflicting drug pricing between Micromedex Redbook and Medi-Span was encountered, the prices provided by Medi-Span were used. Because this study used publicly available data and did not contain any patient-or individual-level data, it was considered to be exempt from institutional review board approval based on the Common Rule. This study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline.

JAMA Network Open | Oncology
Average wholesale price describes the average price paid by retail pharmacies for a drug from the wholesaler and is used by insurers to determine the reimbursement of prescription drugs.
Wholesale acquisition cost is the manufacturer's list price when the drug is sold to the wholesaler and subsequently distributed to health care institutions. Average wholesale price and WAC pricing presented in the

Statistical Analysis
The primary outcome was the trend over time in AWP and WAC unit prices and the strength of the linear association between prices of drugs among the multiple brand-name medications within each therapeutic class. Price correlations were measured using the Pearson correlation coefficient. In addition, the compound annual growth rates (CAGRs) for brand-name medication costs within each therapeutic class were calculated. Compound annual growth rate denotes the mean annual increase for all classes, the average yearly inflation rate of 1.75% during the same period. Of note, among all therapeutic classes studied, there was only 1 price decrease. This was observed for erlotinib between 2019 and 2020, and it corresponded with the introduction of a generic competitor to the market.

Discussion
This cross-sectional study found a positive correlation between high list prices among different drugs within the same class on the market across 5 therapeutic classes used for metastatic NSCLC from 2015 to 2020 in the US. These results suggest that there was little price competition among the manufacturers of these products. This is consistent with previous findings that little difference exists in the median wholesale price of novel drugs and next-in-class drugs. 2 Although one might expect oncology drug prices to decrease over time after market entry, the list price of most anticancer agents increases paradoxically. An earlier study of 24 patented injectable anticancer agents in the US demonstrated that prices increased by 25% over a period of 8 years after launch; these increases in cost were not offset by supplemental US Food and Drug Administration approvals, new competitors, or new off-label indications. 3 Thus, price increases over time were not substantially reduced by market competition and increased at similar rates among drugs within the same class.
Among the agents studied, we identified only 1 instance of a decrease in price, which coincided with the introduction of a generic formulation. However, in general, the introduction of generics does not substantially change the cost of cancer therapy. 4 For example, when generic imatinib was introduced, its monthly sales price was only 8% less than the price of the brand-name imatinib.
Despite this small reduction in price, generics offer the promise of lowering prices and making drugs more affordable for patients. Reduction in drug costs over time with the use of generics can improve cost-effectiveness, change reimbursement decisions, and increase the number of treatment options available to patients. 5 Although generics offer the promise of lowering prices, there are numerous instances when generic competition is delayed or when manufacturers extend patents or develop more convenient dosage forms to keep market share. 6 With the exception of the immunotherapy class (median CAGR, 1.81%), the median cost CAGR outpaced the annual growth rate of the consumer price index for prescription drugs at 2.10% and, for all classes, the average yearly inflation rate of 1.75% during the same period. This may have been attributable to an increasing number of immunotherapy drugs in the pipeline and an expanding number of indications, which may allow drug manufacturers to keep the prices lower compared with the other targeted agents. Furthermore, given the global approvals of immunotherapy agents, the vast global market share may play a role in the lower CAGRs for this class of drugs.
Although AWP and WAC do not always reflect the true net prices paid by insurers or patients, increasing drug prices correlate with higher out-of-pocket expenses for patients. 7 Financial toxicity may be associated with increased symptom burden, worse quality of life, and increased cancer mortality. 8