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Last year, oncologists dealt with the most severe cancer drug shortage to date. Over about 6 months in 2023, cancer centers across the United States struggled to obtain more than a dozen oncology and supportive care drugs, including two mainstays of treatment: Cisplatin and carboplatin.

Cancer centers have grappled with intermittent drug shortages for several decades but "nothing rivaled this," said Elizabeth A. Guancial, MD, a medical oncologist at Florida Cancer Specialists & Research Institute, Sarasota, Florida.

Although the major shortage issues have eased since August 2023, anxiety surrounding the crisis has not.

This drug shortage is not the first — and experts warn that it won't be the last.

"While no one wants this repeated, we have to acknowledge that given the complexity of the state of drug production and access," Guancial said, "this is something we will face again in the future."

Successfully navigating future shortages will require a multipronged approach, including timely notification of impending shortages, said Guancial, who outlined how the crisis unfolded for Florida Cancer Specialists and how the center managed.

An Unprecedented Crisis

The US Food and Drug Administration (FDA) first reported shortages of cisplatin and carboplatin in February 2023. On its website, the FDA listed the shortage of cisplatin on February 10 and the shortage of carboplatin on April 28.

But the drug shortage announcement came with few specifics, including no estimated duration, Guancial recalled.

These platinum agents are used to treat 12 cancer types, including breast, head and neck, lung cancer, bladder, and prostate cancer, in dozens of regimens.

"Caring for patients with cancer during the platinum shortage was an extremely challenging experience," said Guancial, who shared her cancer center's experience during a recent American Society of Clinical Oncology (ASCO) symposium earlier this year.

At the start of the crisis, patients and oncologists were being inundated with ads for costly biological agents and new therapies for other diseases, yet inexpensive life-saving cancer medications were in short supply, Guancial recalled.

At Florida Cancer Specialists, the stakes were high. The multisite practice employs about 250 medical oncologists and treats about 1.3-1.5 million patients a year or 550 patients with carboplatin and 250 with cisplatin weekly.

The center's first order of business: Supply preservation.

To preserve the platinum supply for as long as possible, "our pharmacy team automatically began rounding down doses for all patients receiving palliative-intent therapy by 5%-10%," Guancial explained.

With more than twice as many patients requiring carboplatin, physicians also identified those eligible to switch from carboplatin to cisplatin and notified them. But in most cases, Guancial said, such a switch was inappropriate due to contraindications.

On April 7, without any news about future drug availability, efforts to expand the dose reduction protocol to patients undergoing curative-intent treatment began.

By April 28, with only a week's supply on hand, the Florida Cancer Specialists learned that carboplatin was unavailable for purchase.

To make matters worse, the team only had a 3-week supply of cisplatin left, "due in part to the increased weekly usage as we transitioned patients from carboplatin to cisplatin," Guancial said. "Sequencing and scheduling took on central importance."

When possible, the team tried to increase the time until patients needed carboplatin or cisplatin regimens.

For patients receiving curative-intent neoadjuvant therapy for bladder cancer, for instance, Guancial's oncology team partnered with a nephrologist to try to move up scheduled cystectomy dates and have patients temporarily stop their platinum regimens and then resume after the procedure.

For patients with gynecologic malignancies, the team tried to move up debulking surgeries.

For patients with breast cancer needing perioperative platinum-based therapy and neoadjuvant anthracycline-based regimens, the team switched the order of treatment, so patients received anthracycline-based therapy first.

And for palliative-intent therapy, instead of 3-week cycles, "could we stretch it to 4 or maybe even 5 weeks in some cases?" she said.

The hope was that these platinum agents would be available by the time patients needed them, she explained.

On May 3, physicians on the center's therapeutics committee led an effort to modify the center's formulary to provide guidance on drug substitutions.

For instance, the center began offering pembrolizumab plus enfortumab vedotin for locally advanced or metastatic bladder cancer, although the FDA's approval for this indication would happen about 6 months later.

Fortunately, insurers approved the alternative therapy during this 6-month period before the official FDA approval occurred. "Many of our patients are still benefitting from that treatment 6 months later," Guancial said.

By the end of May, the center restricted use of both carboplatin and cisplatin to patients undergoing curative-intent treatment.

"This was also, in some ways, a grim turning point," Guancial added. "Up until this point, we had been able to get by rounding down doses, extending cycling, maybe even offering platinum with every other cycle with a palliative doublet treatment, but we were still able to give most patients some [platinum]."

On the brighter side, the conservation strategies employed early on helped the center develop an effective and evolving approach to rationing care.

"I think it underscores the point that the earlier we're notified about shortages, the sooner we can modify usage patterns to prioritize patients who have potentially curable disease," Guancial said.

Tough Conversations and a Turning Point

During the worst points of the drug shortage, oncologists had tough conversations with their patients.

Guancial explained that patients needed to be informed that the center did not have the main therapies we needed to treat them, and we did not know when we would again.

However, June 15 brought signs of hope. The first delivery of cisplatin from China arrived — a temporary stopgap measure the FDA permitted to help ease the shortage.

On July 7, carboplatin became available in limited supply, allowing treatment of a limited population of patients with gynecologic malignancies and small cell lung cancer.

On July 24, all restrictions for cisplatin were lifted. Eleven days after, on August 4, all restrictions for carboplatin were lifted.

Many "weeks and thousands of patients later, we finally had unrestricted usage of carboplatin and cisplatin again," Guancial said.

Although the worst of the crisis is over, as of last month, the FDA still lists about 16 commonly used oncology drugs as "currently in shortage" or with limited availability, including capecitabine, methotrexate, vinblastine, as well as carboplatin and cisplatin.

An American Cancer Society Cancer Action Network survey conducted in September 2023 also found that cancer drug supply issues have persisted beyond the summer, with 1 in 10 cancer centers reporting impacts to care such as difficulties findings substitute medications and treatment delays.

Even for those no longer facing supply challenges, the effects of the carboplatin and cisplatin shortages have lingered.

For Florida Cancer Specialists, costs skyrocketed as the center pivoted to different protocols, suppliers, and drugs, while reimbursement for drugs remained the same.

Many patients and clinicians continued to experience fear and anxiety from the unplanned treatment changes and the ethical and moral dilemmas surrounding drug rationing decisions.

Another concern, Guancial said, was not knowing how rationing and delaying care over 6 months affected patient outcomes.

The answer to that question is "weighing on all of us," she said.

Managing Future Shortages

In late November 2023, ASCO published updated guidance for navigating patient care during an oncology drug shortage.

The guidance, which covered dozens of clinical situations involving different cancer types, endorsed many of the strategies Guancial had used at her center. These strategies included prioritizing patients undergoing curative-intent therapy, minimizing waste through dose rounding, increasing intervals between cycles, decreasing doses, altering drug sequences, and using substitutes when appropriate.

Guancial highlighted the need for strong communication and collaboration between oncologists, pharmacists, patients, and guideline bodies to help successfully navigate drug shortages.

Patient-centered advocacy groups should also have a seat at the table, according to cancer survivor and patient advocate Rick Bangs. Advocacy groups can, for instance, help educate patients about the shortage and how to navigate it and help oncologists improve their communication with patients, Bangs explained.

Advocacy groups should participate in guideline development and revision processes, Bangs added, and can play an important role in helping craft legislation that builds protections against future shortages.

For its part, the FDA already addresses drug shortages in several ways, including requiring manufacturers to notify the agency of supply disruptions, delays, and discontinuations and allowing flexibility on importing drugs from other countries, according to Chana Weinstock, MD, team leader for genitourinary oncology in the FDA Office of Oncology Products.

In 2019, the FDA published a report on drug shortages, exploring root causes, such as a lack of incentives for drug manufacturers to produce less profitable generic drugs, as well as potential solutions, such as providing financial incentives to companies to manufacture generic drugs.

But there are limits to what the FDA can do.

For instance, "we can't require a company to make a drug, we can't require a company to make more of a drug" or to have "a diversified supply chain for a given drug," Weinstock said.

To address an inevitable future drug shortage, chronic supply chain and manufacturing roadblocks would need to be addressed to remedy the production issues that plagued the recent shortage.

"This is not trying to do something that is somehow impossible with manufacturing. These are generic drugs that should be able to be produced safely, easily, and with adequate supply," Maurie Markman, MD, from the City of Hope, Duarte, California, said in a recent video commentary for Medscape Medical News. "We have simply got to come up with a system that makes it work for all of us and all of our patients."

Guancial reported receiving honoraria from Research to Practice. Bangs reported a consulting or advisory role for Nonagen Bioscience and other relationships with the Bladder Cancer Advocacy network, National Cancer Institute, and SWOG. Weinstock reported having no disclosures.

Sharon Worcester, MA, is an award-winning medical journalist based in Birmingham, Alabama, writing for Medscape Medical News, MDedge, and other affiliate sites. She currently covers oncology, but she has also written on a variety of other medical specialties and healthcare topics. She can be reached at sworcester@mdedge.com or on X: @SW_MedReporter.