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The nation's cancer centers continue to grapple with shortages of commonly used oncology drugs, according to a new survey.

Overall, 89% of centers that responded to the survey reported shortages of one or more chemotherapy drugs, the (NCCN) reported. That compared with 93% of respondents to a . The 2024 survey included 28 of NCCN's 33 member institutions.

The characteristics of the shortage changed from a year ago, when platinum agents dominated the list of drug shortages, with more than 90% reporting shortages of carboplatin and 70% of cisplatin. The showed that 11% of centers reported shortages of carboplatin and 7% for cisplatin. The 2024 shortage list had vinblastine at 57%, etoposide at 46%, and topotecan at 43%.

"Critical drug shortages were not a new problem last year and they continue to be a problem now," said NCCN CEO Crystal S. Denlinger, MD, in a statement. "The dual carboplatin and cisplatin shortage was particularly severe, and we were able to help sound the alarm during its peak."

"Despite the renewed attention to drug shortages over the past year, 89% of the responding centers in the latest survey are still reporting shortages of various important anticancer agents," she continued. "Most of them are still managing shortages for more than one type of medication right now. These shortages not only put a burden on patients, caregivers, and providers, but they could also delay vital clinical trials and slow the pace of progress for new cancer therapies."

The current survey identified shortages of 16 different drugs, many of which represent crucial backbone components for multidrug chemotherapy regimens, including dacarbazine (18%), 5-fluorouracil (14%), methotrexate (14%), leucovorin (7%), and hydrocortisone (4%).

Despite the widespread shortages, 93% of centers were able to treat all patients currently receiving a drug in short supply, 56% with mitigation strategies (such as changes in dose or schedule) and 37% without. Additionally, 43% of responding centers reported an adverse effect of drug shortages on participation in clinical trials.

Coinciding with the 2023 survey, NCCN released a for mitigating the effects of drug shortages:

• A regulatory environment that affects a steady supply of core anticancer drugs
• An "ethical and moral obligation" of the pharmaceutical industry to assure a steady supply of core anticancer drugs
• Judicious use of available supplies of anticancer agents, prioritized by efficacy, safety, and cost
• Payers must put patients first and provide flexible and efficient coverage systems that accommodate alternative therapies to replace drugs in short supply

'Brittle' Supply Chain, Low-Ball Pricing

The 2024 American Society of Clinical Oncology (ASCO) meeting included a session devoted to drug shortages, delving into the key contributing factors. In her introduction of the panel, ASCO chief medical officer Julie Gralow, MD, pointed out that drug shortages in oncology are not new.

"Those of you in the room likely know that while we had very acute drug shortages this past year, these drug shortages in oncology, and broader than oncology, have been going on for 10 to 15 years," she said. "ASCO started with drug shortages webinars back in 2011, when we had some very severe shortages of pediatric cancer drugs."

A key factor in shortages relates to the "brittleness" of the supply chain structure, said Alex Oshmyansky, MD, PhD, of Mark Cuban Cost Plus Drugs in Dallas.

"Even if the active pharmaceutical ingredients are made in a high-regulatory jurisdiction, such as Western Europe and North America, a lot of the key starting materials that are common to all of them are generally made in the same facilities in China," he said. There was a shortage this past year when one machine broke in a plant in central China, he added, "and it just sort of cascaded throughout the entire world."

"It hasn't really changed over the past 10, 15, 20 years," Oshmyansky continued. "It seems to be relatively stable, and it doesn't seem like there's much of a motivation to change that."

Following up on Oshmyansky's comments, FDA commissioner Robert Califf, MD, said, "We're way too dependent on China for our basic materials for generic drugs. We have a market failure in the way contracting has been done, in my view, and the unwillingness of health systems and cancer centers to pay a fair price for the product that's needed and contract quality into the system."

"I would like ASCO to look within itself a little bit and ask the question, 'What can we do when we contract for generic drugs, to write contracts that actually pay a fair price, so that people can make them and have a quality system of production?'" he continued. "A lot of it is a general relationship. The lower the cost of the product, the greater likelihood of shortage. That's kind of crazy, but that happens a lot when the price of the product is below the cost of making it with quality."

Not a Passing Storm

During the 2011 shortage of several key injectable drugs in pediatric oncology, many people thought it was a "storm that will pass," said Allan Coukell, BScPharm, of Civica Rx in Lehi, Utah, a nonprofit generic drug company "created specifically to respond to drug shortages.

"I think the biggest change is that policymakers and providers are recognizing that shortages are an output of the way we buy generic drugs," said Coukell. "If we don't change our behavior, we will continue to have shortages, and by any measure, they're worse now than they've ever been. The American Society of Health System Pharmacists recently put out a report that had 320 drugs in shortage."

The Civica business model includes components such as buffer inventory, selection of suppliers for quality, and long-term contracts to stabilize the marketplace.

"There's starting to be a recognition among policymakers that we need to move in that direction," said Coukell. "What keeps me up at night is that we don't need to wait for Congress to act. We could move in that direction now, but we're not seeing as much movement as we should."

Another contributing factor is the lack of depth in the manufacturing community, said Michael Sargent, of the Association for Accessible Medicines in Washington.

"Every year we look at shortages data, and we look at pricing and contracting trends," he said. "Over 80% of the products currently in shortage are multi-source generics, and over 50% of those are priced at $1 or below per unit. When you talk about trying to create stability and sustainability across the marketplace, what we see is the most acute shortages, the ones that have the most impact on health systems, are the ones where there's a real low concentration or consolidation in the marketplace."

"When you have a high number of approved generics but a low number of manufacturers, from our point of view, that has everything to do with pricing and contracting," he added.

An early warning system for impending drug shortages would appear to be desirable, but in fact, making information about looming shortages widely available could actually make the situation worse, said Marta Wosinska, PhD, of the Brookings Institution in Washington. She said she gets nervous giving this kind of information to hospitals because an early warning of a shortage can prompt them to buy and stockpile as much of a drug as they can.

The shortages of cisplatin and carboplatin offer a case in point, Wosinska continued. Hospitals that were carefully following market trends "went on a shopping spree. They went from a couple of weeks of inventory to sitting on 6 months of these drugs. While the smaller independent and community centers were like, 'What just happened? I can't find product anywhere.'"

She drew an analogy to the toilet paper shortage during the pandemic.

"There was actually a pretty good amount of toilet paper. It's just that everybody needed to have a lot more of it at home, and it basically precipitates the shortage. For that reason, I've been really opposing a kind of early warning system to buyers because it actually can make things worse."

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