2023 Chemotherapy Shortages Drove Altered Treatment Plans, Persistent Cost Increases

The 2023 cisplatin shortage in the United States (US) led to shifts toward the use of alternative chemotherapy agents for the treatment of patients with head and neck cancer, as well as increased overall and per-administration costs of chemotherapy agents, according to findings from an analysis presented at the 2024 ASCO Quality Care Symposium.¹

During the drug shortage period, which study investigators defined as February 2023 through August 2023, the use of cisplatin at the oncology centers included in the study decreased by 15%. Conversely, during the shortage, these centers increased their use of carboplatin, paclitaxel, cetuximab (Erbitux), and fluorouracil by 40%, 24%, 15%, and 5%, respectively.

“We observed significant changes in the overall administration patterns in several drugs used for routine treatment of [patients with] head and neck cancer,” study author Jody S. Garey, PharmD, director of Clinical Analytics & Data Science at McKesson, stated during the presentation. “Notably, the timing of these changes occurred beginning in May 2023, nearly 4 months after the cisplatin shortage was announced, suggesting that supply may have been more readily available early on.”

Garey also noted that cetuximab administration rates remained elevated after the shortage compared with prior to the shortage. Additionally, investigators observed a pronounced shift in drug use patterns for patients starting new treatments during this time frame; however, they confirmed that this trend was consistent with those seen for all lines of administration.

Furthermore, most treatment changes within the shortage period occurred in the curative-intent setting. During the shortage, in the palliative setting, investigators observed increases in cetuximab and paclitaxel use alongside decreases in carboplatin and fluorouracil use. Garey noted that in addition to carboplatin and fluorouracil being managed as short-supply drugs, the decrease in the palliative use of these agents represents a potential shift toward the reserve of these therapies for use in the curative setting.

A Significant Series of Shortages

“Drug shortages have increasingly become a normal problem to solve in the delivery of health care across the US,” Garey said.

During the second quarter of 2023, the US experienced 309 active, ongoing drug shortages—the highest number of drug shortages in approximately a decade, and close to the all-time high of 320 shortages.² Moreover, in July 2023, a report on the severity and impact of drug shortages published by the American Society of Health-System Pharmacists (ASHP) revealed that 57% of participating ASHP members (n = 1123) who responded to a survey conducted from June 23, 2023, to July 14, 2023, reported that they experienced “critically impactful” chemotherapy shortages.

“The downstream impact of drug shortages has been reported to impact all aspects of care delivery throughout the supply chain,” Garey emphasized.¹ “Cisplatin is the cornerstone of treatment for many different types of cancer, including head and neck cancer. Drug shortages endanger the health care system.”

On February 10, 2023, the FDA announced a shortage of cisplatin caused by manufacturing disruptions. That month, cisplatin was place on the Fair Share (FS) Program, which is designed to promote equitable distribution of existing drug supplies across oncology practices based on historical usage patterns, as well as reduce reactive drug purchasing. Cisplatin remained on the FS Program until October 2023.

In March 2023, paclitaxel was also placed on the FS Program until April 2023, and in April 2023, fluorouracil and carboplatin were placed on the FS Program until September 2023 and January 2024, respectively. Additionally, in April 2023, The US Oncology Network Pathways and Task Force Committee published guidelines to reserve cisplatin supply for curative-intent treatment.

Study Design

In this analysis, investigators described how the cisplatin shortage affected the treatment of patients with head and neck cancer at practices in The US Oncology Network. Trends in chemotherapy use before, during, and after the shortage were analyzed in terms of overall use, new treatment starts, and treatment intent. The shortage’s effect on costs, including payer impact and estimated patient payment responsibility, was also assessed.

In the study, the pre-shortage time frame was defined as July 2022 through January 2023. The time frame during the shortage was defined as February 2023 through August 2023. The post-shortage time frame was defined as September 2023 through March 2024.

Drug administration records from the electronic health record were used to evaluate patterns of chemotherapy administration and treatment intent throughout the study period. Administrations were studied as a whole and by patients’ first administration to assess new treatment starts. Provider–documented information about line of therapy was used to assess treatment intent, which was further classified as curative or palliative.

This study used financial claims for each administered chemotherapy from a financial data warehouse based on billed chemotherapy amounts. Costs were adjusted to Medicare-allowable amounts.

Effects on Guideline-Concordant Care

Referring to the National Comprehensive Cancer Network (NCCN) Guidelines for the management of head and neck cancers that were available during the shortage period, investigators noted that the NCCN-recommended chemotherapy regimen with the greatest increase in curative-intent use during the shortage was carboplatin plus paclitaxel, which carried a Category 2b recommendation at the time. This indicates that the cisplatin shortage resulted in less guideline-concordant care.

Furthermore, although most agents used in the palliative setting in this investigation carried NCCN Category 1 or 2 levels of evidence, the choice of agent may have greatly affected treatment costs, Garey explained.

Investigators also observed increases in total treatment costs and average drug costs per administration during the shortage period compared with the pre-shortage period. These costs remained elevated in the post-shortage period, which Garey reported was likely because of treatment continuation.

Financial Implications and Next Steps

To evaluate the financial implications of cost trends on individual patients, investigators estimated patient cost-sharing amounts of the alternative drugs used during the shortage based on example commercial and Medicare scenarios.

For cisplatin, carboplatin, paclitaxel, carboplatin plus paclitaxel, 5-fluorouracil (5-FU), carboplatin plus 5-FU, and cetuximab, the respective average Medicare-allowable reimbursements were $18.00, $14.00, $16.00, $30.00, $22.00, $36.00, and $2607.00. The patient-responsible payments for a Medicare plan without secondary coverage for these respective drugs were $3.60, $2.80, $3.20, $6.00, $4.40, $7.20, and $521.40.

“[We] observed an increase in overall cost and average cost per administration that extended to both payers and patients. These results continued even after the shortage was over,” Garey noted.

Using an example of a commercial insurance plan with a $3000 deductible, 20% coinsurance, and a $6000 out-of-pocket maximum payment, the patient-responsible payments for these respective agents were $21.60, $16.80, $19.20, $36.00, $26.40, $43.20, and $3025.68. Overall, investigators noted that although costs were generally increased for combination therapies vs single-agent therapies, the major impact on patient responsibility was observed with the use of cetuximab, which does not have generic or biosimilar availability.

“It’s critical that as an oncology community, we continue to investigate and report the impact of drug shortages. The cisplatin shortage, which we all experienced, is the opportunity to have a call for action…to partner with available advocacy groups and members of the supply chain, including the FDA, to work toward a long-term solution to end drug shortages,” Garey concluded.

References

1. Indurlal P, Garey JS, Albaugh J, et al. Prescription predicament: unveiling the financial fallout of drug shortages. JCO Oncol Pract. 2024;20(suppl 10):1. doi:10.1200/OP.2024.20.10_suppl.1
2. Severity and impact of current drug shortages. American Society of Health-System Pharmacists. June/July 2023. Accessed October 8, 2024. https://www.ashp.org/-/media/assets/drug-shortages/docs/ASHP-2023-Drug-Shortages-Survey-Report.pdf