As Cancer Drug Shortages Increase, Patients’ Lives Are at Stake

Oncology leaders recently testified before a House subcommittee about how cancer drug shortages are hindering cancer care in the United States and threatening the lives of patients.¹

Both leaders stressed the need for long-term solutions to resolve and prevent drug shortages that have plagued health care for years but have become more severe as of late.

“This is a growing crisis for cancer patients. As a result of these drug shortages, Americans with cancer are facing treatment delays, potentially receiving inferior treatments, and even having their treatments stopped,” said Ted Okon, executive director of Community Oncology Alliance, when testifying before the House Committee on Energy and Commerce: Subcommittee on Health.²

“Our inaction in fundamentally solving the cancer drug shortage problem, which has existed for years but is now the most severe that we have ever faced, has already likely signed a death sentence for some Americans,” Okon added.

In her testimony, Julie Gralow, MD, chief medical officer of the American Society of Clinical Oncology (ASCO), called the current shortages “the worst I have seen in my 30-year career.”³

“[W]e’ve estimated that between 100,000 and 500,000 US patients are impacted or have the potential to be impacted if this keeps going for several more months,” Dr Gralow said in a separate interview.

There are 14 cancer drugs currently in short supply in the US, according to the US Food and Drug Administration’s (FDA) drug shortage website.⁴

A recent survey of National Comprehensive Cancer Network member institutions suggested that cancer centers have been hit particularly hard by the shortages of carboplatin and cisplatin.⁵ Carboplatin was in short supply at 93% of the cancer centers surveyed, and cisplatin was in short supply at 70%. Though the cisplatin shortages did not interrupt patients’ treatment, the carboplatin shortages forced oncologists to modify treatment for some patients.

“That’s a difficult decision to make with your patients, and it forces cancer centers and practices like mine to establish rationing policies,” said Ray Page, DO, PhD, president of the Center for Cancer and Blood Disorders in Weatherford, Texas.

Dr Page noted that carboplatin and cisplatin are generic drugs that are not difficult to manufacture and are generally inexpensive. “In so many cancers, they are the backbone drugs of combination chemotherapy, and, for many of those situations, those drugs are given with curative intent,” he said.

Short-Term Responses to Current Shortages

Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence, said the FDA will continue to use all tools available to mitigate and prevent shortages, including, “using regulatory flexibility such as temporary importation of overseas supply to meet patient needs after careful evaluation of that supply to ensure no risks to patients.”

“The agency does not manufacture drugs and cannot require a pharmaceutical company to make a drug, make more of a drug, or change the distribution of a drug, but we are working closely with numerous manufacturers and others in the supply chain to understand, mitigate, and prevent or reduce the impact of intermittent or reduced availability of certain products,” Dr Pazdur said.

The FDA is currently working with the Chinese manufacturer Qilu Pharmaceuticals and the Canadian company Apotex Corp. to temporarily import cisplatin.⁶ Some cisplatin is currently available from WG Critical Care, Teva, and Hikma, according to the American Society of Health-System Pharmacists (ASHP).⁷ The ASHP website also has details on the status of carboplatin and other drugs in short supply, including methotrexate and fluorouracil.^8-10

In the meantime, ASCO and the Society of Gynecologic Oncology have issued clinical guidelines to help oncologists navigate the shortages of carboplatin, cisplatin, fluorouracil, and methotrexate.^11,12

Causes of Shortages and Long-Term Solutions

At the House subcommittee hearing, Dr Gralow said the causes of drug shortages “are multifaceted…. Factors such as manufacturing disruptions, quality control issues, regulatory challenges, supply chain vulnerabilities, and market dynamics contribute to the persistent shortage of critical cancer medications.”³

Therefore, Dr Gralow said, resolving shortages requires a comprehensive approach. She laid out a number of recommendations to help address the current shortages. She recommended incentivizing advanced manufacturing technology for critical drugs and active pharmaceutical ingredients (APIs) in both foreign and domestic facilities.

Dr Gralow also recommended stronger notification requirements for manufacturers, not only for disruptions but for their potential impact. She noted that the carboplatin and cisplatin shortages, which were caused by quality control issues at one of Accord Healthcare’s API manufacturers in India, emphasize the need for greater transparency.

Companies are required to notify the FDA of supply disruptions, but there is no law that requires companies to notify the agency of increased demand. While ASCO was aware of the site halting operations, the society did not know the full effect on the supply chain until it began hearing from its members who were not able to acquire the therapies. 

“Even though it was known that this API site was shut down for quality issues, the impact of how much of our imported drug relied on that one site was not known,” Dr Gralow said. “There’s no transparency there.” 

During his testimony, Okon said a key cause of the shortages is the financial challenges that generic drug manufacturers are facing.² He specifically cited Medicare’s Part B drug reimbursement system, which caps drug prices and is also used by commercial payers. He said that mandatory 340B drug pricing discounts and Medicare rebates “erode drug prices,” and the Inflation Reduction Act drug price inflation caps “further put downward pressure on injectable generic drug prices.”

“These products, at best, are so unprofitable that there is little to no margin to invest in manufacturing upgrades,” Okon said in his testimony. “At worst, there is little manufacturing redundancy as manufacturers leave the market.”

Okon called for legislation removing price caps, discounts, rebates, and regulation. He warned that shortages will only worsen if these steps are not taken.

“This is very simple and does not require a PhD in economics: If a generic drug manufacturer cannot make a profit on a drug, they will simply stop making the drug. If a manufacturer makes a very small margin on the drug, it will cut costs, however possible,” he said.

While the hearing did not focus on specific legislation addressing drug shortages, Rep. Cathy McMorris Rodgers (R-WA), chair of the full committee, said she welcomes a discussion on it with her Democratic colleagues and that the problem “must be addressed.”¹³

She and Senate Finance Committee Ranking Member Mike Crapo (R-ID), issued a bicameral request for information to experts and stakeholders on drug shortages.¹⁴

Dr Gralow noted that Republicans and Democrats have different opinions on the solutions to this crisis but said she came away from the hearing feeling both are committed to addressing it.

“They have slightly different ideas about what was needed, the amount of help regulation would have versus the market, but it was very uplifting to see them agreeing that they were going to work together because this is a huge problem,” she said.

Disclosures: Dr Page disclosed relationships with G1 Therapeutics, E.R. Squibb Sons, LLC, Gilead Sciences, Takeda, AstraZeneca, Genentech, Roche, Janssen, Celgene, and Lilly.

References

1. Legislative solutions to bolster preparedness and response for all hazards and public health security threats. United States House of Representatives Energy & Commerce Health Subcommittee. Published June 13, 2023. Accessed June 22, 2023.

2. Testimony of Ted Okon. Legislative solutions to bolster preparedness and response for all hazards and public health security threats. United States House of Representatives Energy & Commerce Health Subcommittee. Published June 13, 2023. Accessed June 22, 2023.

3. Testimony of Julie R. Gralow. Legislative solutions to bolster preparedness and response for all hazards and public health security threats. United States House of Representatives Energy & Commerce Health Subcommittee. Published June 13, 2023. Accessed June 22, 2023.

4. Current and resolved drug shortages and discontinuations reported to FDA. US Food and Drug Administration. Accessed June 22, 2023.

5. Carboplatin & cisplatin shortage survey results. NCCN Best Practices Committee. Published June 7, 2023. Accessed June 22, 2023.

6. Chinese company may help ease US shortage of cisplatin. HealthDay via Cancer Therapy Advisor. Published June 7, 2023. Accessed June 22, 2023.

7. Cisplatin injection. Current drug shortages. American Society of Health-System Pharmacists. Published June 20, 2023. Accessed June 22, 2023.

8. Carboplatin solution for injection. Current drug shortages. American Society of Health-System Pharmacists. Published June 12, 2023. Accessed June 22, 2023.

9. Methotrexate injection. Current drug shortages. American Society of Health-System Pharmacists. Published June 16, 2023. Accessed June 20, 2023.

10. Fluorouracil injection. Current drug shortages. American Society of Health-System Pharmacists. Published June 20, 2023. Accessed June 22, 2023.

11. Clinical guidance. Drug shortages. American Society of Clinical Oncology. Accessed June 22, 2023.

12. Chemotherapy drug shortage. Society of Gynecologic Oncology. Accessed June 20, 2023.

13. Chair Rodgers: America must be ready to respond to all public health threats. Energy and Commerce Committee. News Release. Published June 13, 2023. Accessed June 22, 2023.

14. Chair Rodgers, Ranking Member Crapo issue request for information to inform policymaking on drug shortages. Energy and Commerce Committee. News Release. Published June 12, 2023. Accessed June 22, 2023.

This article originally appeared on Cancer Therapy Advisor