Sabari on the Growing Impact of Drug Shortages in the Oncology Space

Joshua K. Sabari, MD

Healthcare systems have been combatting the shortages of certain oncology drugs for years. However, the COVID-19 pandemic made the problem an even bigger challenge, leaving more patients without medication or with a delay of treatment.

Currently, the oncology space is short on supply of 11 chemotherapy agents, as well as a prostate-specific membrane antigen targeted therapy. Two of the most depleted therapies include carboplatin and cisplatin.

Now, more experts in the oncology space are calling for action to help address this problem.

In an interview with Targeted Oncology^TM, Joshua K. Sabari, MD, medical director of Kimmel Pavilion 12 at NYU Langone Health’s Perlmutter Cancer Center and assistant professor of medicine at NYU, discussed drug shortages and how they are affecting clinicians and patients in the oncology space.

Targeted Oncology: How did the shortage for cancer drugs start?

Sabari: Drug shortages are not new. They've been around for a long time, and we have seen [it] in lots of different fields, ICU care, infectious disease, and clearly in oncology, a very niche space. We've seen significant drug shortages for the past 5 or 10 years. But ever since COVID and supply chain issues, we've seen an increase. There's about a 20% or 30% increase in current shortages. Really, it's 1 pharmaceutical company that produced carboplatin that had quality control issues, and the FDA fortunately shut them down, and that led to a major shortage.

It shows you the weak points in generic therapeutic medications. A lot of medicines that are on patent and are being produced by pharmaceutical companies, those medicines do not go on shortage, and we don't have sort of limited supply there. But it's really these medicines that are generic, that are off patent, that have very low margins. These are medicines that oftentimes are at risk of going into shortage, and that's what we've seen with carboplatin and cisplatin of late. But again, this is not a new issue. I think the closure, or the suspension of carboplatin from Intas Pharmaceutical Limited, has sort of highlighted this as an issue.

Where do we go from here now that different drugs aren't available right now?

For oncology, specifically thoracic medical oncology and some of the other solid tumors, carboplatin has been a major issue. We know that carboplatin is a standard of care agent in curative intent, adjuvant therapy for thoracic malignancies, as well as ovarian cancer. This is a drug approved in the metastatic setting in other histologies as well, such as head and neck cancer, breast cancer, colorectal and others. Thinking about how we move forward with a lower sort of availability of these agents for our patients, we need to reprioritize nonessential use of these therapies, particularly given the limited supply. If there's an alternative agent available for our patient, we should use that agent.

In the metastatic setting, there are regimens that don't require a platinum backbone. For example, a CTLA4 inhibitor and a PD-1 inhibitor. One should consider that as an option to increase the supply of this medication. Another thing to consider is to use other medicines where carboplatin may be able to be replaced by cisplatin. In patients who are fit have good renal function obviously and don't have any hearing issues or hearing loss, we do try to use this plant and if available over carboplatin.

We also know that cisplatin is in shortage though at the moment, we also are thinking about increasing the interval between cycles to reduce the total treatment dose when this is acceptable. In the adjuvant or curative intent setting, I highly recommend against changing the dosing or the guidelines. If you look at the ASCO or NCCN guidelines, if the guidelines allow for either a 3- or 4-week infusion, I would recommend considering a 4 week infusion over a 3 week infusion as to allow us to have more supply for our patients. Unfortunately, a lot of vials of medication are utilized 1 time per patient. If we can look at vial optimization, vial size as well as dose rounding and potential opportunity, we moved away from multi-use vials, but if we could move back towards that to save drugs, I think that could be an effective strategy for our patients.

Lastly, I've been seeing this a lot in the New York area. There are some weeks where our center has an excess or vials of carboplatin and we're able to treat patients and there are other weeks where we don't, so thinking about getting patients the best possible care, talking to your colleagues at other institutions where they may not have a shortage or even particularly in other states if feasible, but this is an ongoing issue in oncology I think it's 1 we need to talk to our patients. As a clinician, as an oncologist, it's tough and disheartening to have to make decisions behind who gets a certain therapy and who doesn't. Why does a patient who is 55 and has resected stage III cancer get adjuvant chemotherapy with cisplatin or carboplatin, but someone with metastatic disease is not eligible for carboplatin? I think these are the difficult decisions that hospitals and pharmacy committees are now having to make, and it's tough. I think our government needs to act. ASCO is spending a lot of effort and time on petitioning the government and the FDA to sort of reassure both patients, but also clinicians, and to look at ways that we can plug some of these holes in our infrastructure.

When you are with patients, how do you handle these situations and have these potentially stressful conversations?

I think most patients come into the office hoping to get the best possible therapy they can. When we bring up this idea of there being a shortage, I think patients are usually thrown aback and are often asking, why me? Talking patients through the reasons and the rationale behind why we're tweaking a regimen or why we're changing the regimen is important. If we don't have access to that therapy, we have to think about the next possible alternate therapy that's going to give the patient both the best quality-of-life, but also the best chance at improved survival. I think we're fortunate that we have many different regimens available for our patients. It is unfortunate that we don't have, you know, standard platinum agents, so available as we need. When I have this discussion with patients, I explain to them that this is something that has been changing over the last weeks to months, we may have more supply of the medicine, and we could think about going back to a regimen like that in the near future. But for the time being I explain to them, why other regimens or why other sorts of therapies make sense in this situation. Again, it's an unfortunate thing to even have to have this discussion with our patients in 2023, but it is the reality that we live in,

Are there any steps you believe the FDA should be taking towards figuring out how to deal with these shortages?

I think the FDA needs to be more proactive in understanding if there are issues with quality, and understanding, making sure, and reassuring that there are other suppliers of medications. Lots of times we see generic pharmaceutical companies, or even biotech companies, go out of business. I think those need to be tracked and monitored closely because that affects our national supply chain of these medicines. These are medicines that we depend on a day-to-day basis for our patients. Kudos to the FDA for investigating and assuring that the quality is there for our patients. But I think at the same time, we need to sort of reassure and understand that the supply chain is intact for our patients. All these decisions need to be made, not in a vacuum, but understanding the consequences for our larger population. Kudos to the FDA for really trying to resurrect and sort of incentivize generic pharmaceutical companies to start to produce some of these medications that are in shortage nationally. One amazing thing about our country is that it is a capitalist country and shortages should allow other companies to come in and plug those holes. I think we need to better incentivize them so that we don't run into these ongoing issues.

There's been talk about bringing drugs in from other countries. Do you think that's worth bringing over here considering they have different standards for how things are approved and regulated?

It's a difficult question and a little bit beyond my scope. I think if you're going to import medicines from outside of the United States, you need to have the same quality controls that we do have here in the United States. I'd be concerned about using medicines from other countries that specifically believe they were not sort of upheld to the same rigorous extent of medicines produced here. But if the FDA could audit and sort of investigate other producers of these medications, and they were up to the standard that we expect, I think it would make sense to offload or unburden some of our supply chain issues here. Unfortunately, for carboplatin and some of the other drugs that are in shortage in solid tumor oncology, these medicines are in shortage in other areas of the world as well. So, it's not just a United States problem. It's a global problem in this setting.

What else should be known about these drug shortages?

One thing that we could really think about is equity and thinking about how to promote equitable use of these therapies during these difficult times of shortage. if you're an institution, you should not be making these decisions on your own. I think that leads to burnout, it leads to discontent from an oncologist span standpoint, but also from a patient standpoint, your institution should be developing guidelines for you. There should be committees that approve platinum. Now, anytime someone requests authorization for a platinum agent, it goes through the platinum committee, and they'll give an approval or denial based on the need for that patient. Based on any other alternatives. It's important that these committees be staffed by physicians and not just hospital administrators. Again, I think that is the best way that we're going to be able to provide equitable care for our patients.

I think this affects all of us as oncologists in all the disciplines that we practice in, and community oncologists. This is a real issue on a national as well as a global level. I'm happy that the FDA and ASCO are looking into long-term solutions for this issue.