The High Cost of Shortages of Low-Cost Chemotherapy

What happens when the price of something essential drops so low that few want to make it?

The US health care system found out in the spring and summer 2023, when the fragile ecosystem for manufacturing chemotherapy was disrupted, causing a scramble among cancer centers, practices, and physicians to secure supplies of cisplatin and carboplatin for their patients. During the worst part of the shortage in June and July 2023, physicians swapped the usual drug for a substitute—sometimes one that cost thousands more per dose than chemotherapy, which often costs around $20 a dose.

Jody Garey, PharmD | Image credit: McKesson

This past fall, a study by investigators from McKesson and The US Oncology Network shed light on the full cost of the crisis. Presented at the American Society of Clinical Oncology (ASCO) Quality Care Symposium, held September 27-28, 2024, in San Francisco, the study focused on the replacement of cisplatin in head and neck cancer during the height of the shortage.¹ The McKesson team developed startling data that revealed both the need for policy solutions and lessons for the network’s practices to guard against future disruptions. The findings included the following¹:

• Cisplatin use fell by 15% across the entire shortage for those with head and neck cancer, with a 60% drop during June and July 2023 compared with levels seen before the shortage. Based on average sales price (ASP), the cost per dose of cisplatin was $18 during this period.
• Replacement drugs included carboplatin, which saw a 40% increase in use in head and neck cancer; paclitaxel, a 24% increase; and 5-fluorouracil, with a 5.3% increase. Based on ASP, the cost per dose of these replacements were $14 for carboplatin, $16 for paclitaxel, and $22 for 5-fluorouracil.
• Use of the targeted therapy cetuximab (Erbitux), which does not have a generic option, rose 15% during the shortage. The average cost per dose is $2607.

Typically, protocols call for avoiding a change in therapy once treatment begins. Investigators found that among those taking cisplatin before the shortage, 10% had to shift to a different therapy because the first drug they were taking was not available. Among those who had not started treatment before the shortage, patients instead received carboplatin with or without paclitaxel, 5-fluorouracil, or cetuximab.

In an ASCO statement, the investigators noted that because switching therapies midcourse is not considered standard of care, starting a patient on cetuximab due to the shortage carried a significant financial impact. “All the patients who started cetuximab during the shortage continued to receive the more expensive drug even when the cisplatin shortage ended,” the statement said.²

The 2023 chemotherapy shortage was set in motion after the FDA shut down a generics manufacturer in India that had knowingly violated FDA quality standards. But the larger problem—painfully thin profit margins—had been known to regulators and the broader cancer care community for more than a decade.³

To gain insight into the study and the broader issue, Evidence-Based Oncology (EBO) spoke with Jody Garey, PharmD, director, clinical analytics and data science for McKesson, who is a coauthor on the abstract. Garey, a clinical pharmacist by training, has been with McKesson and The US Oncology Network for 15 years and previously led its Value Pathways. In her current role, Garey uses data generated by the network’s practices through the electronic health record to work on quality improvement, to understand drug utilization patterns, and to help practices participate in programs that have a data component.

EBO: Your bottom line finding showed that when practices had to use cetuximab in head and neck cancer at the height of the chemotherapy shortage, it led to a 16% increase in cost of treating these cancers, which translated in a 144-fold cost increase at the administrative level. Did practices have a sense of how much costs were rising in real time?

Garey: I’m not sure I can specifically speak to what the individual providers or practices thought about as they were making individual patient treatment decisions. Our study really was to evaluate if there was indeed a change in treatment choices and drug utilization, and then to look at the downstream impact in cost based on those treatment decisions. That said, treatment decision-making is very complex. Usually, providers are thinking about what drugs or treatment options have clinical activity and evidence in a particular disease and in a particular treatment setting. Then they evaluate the role of those treatment options, the adverse effects, and, finally, cost may come into play.

In head and neck cancer, in certain circumstances, there really are limited options with available activity for treatment intent to make. As we think about the complexities that were going on at the time from February to April 2023 there were actually other drugs used in head and neck cancer which also were in short supply and being managed as short supply products. That dynamic was incredibly complicated. Those other drugs included paclitaxel, carboplatin, and 5-fluorouracil, and so that also would have been a dynamic to consider as providers are thinking about treatment options.

EBO: We’ve heard from many leaders in community oncology who say this isn’t the first drug shortage—there was a very bad period about 10 years ago—and we don’t seem to have learned anything. Did you glean any lessons from your analysis that can help practices if, unfortunately, another shortage occurs? If so, what learning points can help practices if they go through something like this in the future?

Garey: There are a couple of things in the data that we evaluated. The interesting part is that while the FDA announced the shortage publicly in February [2023], we didn’t actually see a change in utilization for about 3 months. Internally, what that tells us is that we were doing a really good job of trying to manage supply in advance of the official shortage announcement, and even in the early months, I think, in terms of learnings, and this will be a little bit aside from the analysis, but one of the topics that’s been covered around drug shortages is really the reliance of individual entities on each other as a larger ecosystem. Every entity does the best job that they can, and until we’re able to really work together as a community of all suppliers—this is going to be manufacturers, distributors, practices, providers, patients, and the FDA—the problem isn’t going to be holistically solved based on 1 entity.

EBO: It’s similar to what we saw in the pandemic, with the shortages of the personal protective equipment and other supplies.

Garey: You’re 100% correct, and I some of the proactive management during this shortage came out of lessons learned during the pandemic itself.

EBO: The shortage of the chemotherapy cisplatin, and also carboplatin, affected all types of cancer. Why was head and neck your focus for this analysis?

Garey: As you mentioned, there are a lot of discussions around drug shortages and the impact on care, the impact for the ecosystem. But when you look through the data, there’s actually a really surprisingly small amount of objective data showing the impact of shortages on patients or care.
We chose head and neck cancer for several reasons. It’s a population that has a critical dependence on the use of cisplatin. In other cancers, oftentimes, there are alternative options with similar outcomes; in early stages of head and neck cancer, [for] the majority of patients, we saw that intensive treatment is curative and heavily relies on cisplatin. When we evaluated the NCCN [National Comprehensive Cancer Network]guidelines at the time of the shortage, almost all of the options available on NCCN criteria for early-stage disease included cisplatin. So that was really the primary reason we looked at head and neck cancer.

The other piece is that having a shortage of a drug like cisplatin in head and neck cancer could impact long-term outcomes for patients. If an alternative drug has to be chosen, what is the impact on long-term survival, on the ability of patients to reach cure or have long-term resolution of their disease?

EBO: You studied head and neck cancer. We know there were other cancers at that time that were using higher-cost therapies in earlier lines of care, such as the use of antibody-drug conjugates in bladder cancer. In that case a second-line therapy moved into first line. I think you mentioned in your abstract substitutions of more toxic forms of chemotherapy with additional adverse effects. These were not the focus of your analysis, but do you have any sense from talking with the practices of how widespread these cost-driving substitutions were from practice to practice?

Garey: I think cisplatin is certainly not a drug that is only used in head and neck cancer. It’s critical for treatment in many types of cancer—ovarian and gynecologic cancers, lung, testicular cancer, to name a few. Because we focused on the impact in head and neck cancer, I can’t necessarily comment on the use of some of those novel therapies in diagnoses other than head and neck cancer. We actually chose not to look at immunotherapy and head and neck cancer because its role in the diagnosis was evolving, so already on NCCN guidelines in certain scenarios that change was happening rapidly, as well as the emergence of new data.

EBO: As a pharmacist, can you speak to the impact of substitutions, especially with cetuximab, when patients need treatment? Does the practice have to redo a prior authorization? Are there delays, or the need for additional staff time?

Garey: Prior authorizations can absolutely be burdensome in terms of the practice resources required and the time that it takes to get those appropriate approvals. We did not specifically look at whether or not patients were changed mid treatment. In fact, when we looked at utilization patterns and evaluated new treatment, we saw most of the change was happening in the new treatment setting. That said, I think the idea of having to redo prior authorizations is, of course, burdensome, and you want to limit that in all circumstances. The interesting part with the guidance that went out from the P&T [pharmacy and therapeutics] committee to practices was to prioritize cisplatin patients who were already on therapy, as well as scenarios where cisplatin was being used in a curative treatment intent.

EBO: Your abstract mentions that even temporary shortages can have long-term financial implications. Did the shortages cause financial issues for practices that have payment tied to the concordance to a pathway?

Garey: Many of The US Oncology Network practices participate in value-based care programs, and this was really the influence for why we included that statement. Value-based care programs can include total cost of care models. We see this with the Enhancing Oncology Model, the follow-up to the Oncology Care Model. That program started in July 2023, and the program measures total cost of care for enrolled Medicare patients in 6-month episodes. Practices are rewarded for quality performance, as well as lowering the total cost of care compared with nonparticipating practices, and this is evident in terms of a shared savings model. If a practice is forced into a situation where the less expensive drug is not available and only a higher-cost item is available, that impacts their total cost of care for the patients—and it may impact their overall performance in that type of a total cost of care model.

EBO: We haven’t heard as much about the chemotherapy shortage recently. What’s your sense of where things stand?

Garey: In terms of the supply of cisplatin, it has rebounded from the shortage. The network really partners with McKesson on supply of generic drugs, as do many other community providers and institutions. When we think about how things are being managed, certainly the network leverages its P&T committee. Any time there is communication about a drug that either is threatened with short supply or is actively in short supply, the P&T committee is there to have conversations; there’s representation from all the practices to make decisions and recommendations on how to manage it.

EBO: Those sound like a lot of steps to try to make sure you are ahead of the curve on any future shortages. Is there anything else that you would like to add?

Garey: McKesson builds continuous improvement, redundancy, and contingency planning into their system to help provide surety of supply, identify and proactively mitigate points of failure. There are a couple of examples that I can speak to—such as, McKesson tries to diversify its supplier and manufacturer partners, looking at partners who are in multiple geographies in order to optimize the inventory level, secure backup product and alternatives whenever possible, and be in the position to obtain supply for multiple manufacturers. The other example is that they have what’s called a critical care task force that’s implemented, and so this includes a cross-functional team, including clinical pharmacists and supply chain professionals, in order to monitor in a proactive manner, communicate if there are going to be issues, and then respond to supply chain trends and needs.

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):abstract 1. doi:10.1200/OP.2024.20.10_suppl.1
2. New study highlights long-lasting effects of cancer drug shortages. News release. ASCO. September 23, 2024. Accessed November 27, 2024. https://society.asco.org/about-asco/press-center/news-releases/new-study-highlights-long-lasting-effects-cancer-drug
3. Page P. At hearing on recurring cancer drug shortages, rural areas come into focus. Am J Manag Care. 2024;30(5):SP415.