Cisplatin/Carboplatin Shortages Underscore Need for Strategies to Prevent Future Cancer Drug Disruptions

Although the ongoing shortage of cisplatin and carboplatin in the United States has prompted short-term changes and guidelines to address the current situation, long-term strategies and oversight are needed to prevent potential future drug shortages that could affect the treatment of patients with cancer, according to Balazs Halmos, MD.

“This is a wake-up call. We need to figure out how in the United States, [instead of] a patchwork [system] where everyone is looking out for themselves, we can create a national platform to look out for our patients together,” Halmos said.

In an interview with OncLive^®, Halmos explained why a national effort is needed to mitigate current and future drug shortages in oncology and discussed strategies being used to navigate the current cisplatin and carboplatin shortages. Halmos is a professor of medical oncology in the Department of Oncology and a professor of oncology and hematology in the Department of Medicine at Albert Einstein College of Medicine, as well as associate director of clinical science, director of Thoracic Oncology, and director of Clinical Cancer Genomics at Montefiore Medical Center in New York, New York.

OncLive: What challenges have the ongoing shortages of cisplatin and carboplatin presented from a clinical standpoint?

Halmos: There are significant shortages, and as a field, we've been taken by surprise by this. We got into medical oncology believing that our job is to advance science, go from trial to trial, improve our standard of care, and that the drugs that are being developed that improve patients’ lives will be readily available afterward. It's such an incredible, upsetting surprise that this is not the case [right now with cisplatin and carboplatin].

Although there have been a few [drug] shortages here and there over the past few years, those involved drugs were not all that critical or were maybe for niche patient populations, [so some of those shortages] may have been overlooked. Now we realize that there's a major systematic problem as to making sure that there's an appropriate pipeline of cheap oncology drugs that we've developed not yesterday, not 5 years ago, but 40 or 50 years ago. They have been the foundation of cancer care for so many types of cancers.

It’s great that we’re making big advances with new treatments [such as] CAR T-cell therapies, bispecific T-cell engagers, and all kinds of checkpoint inhibitors. They’re fantastic. However, not being able to provide drugs such as cisplatin and carboplatin, which are so critically important for patients with head and neck cancer, lung cancer, all kinds of gynecologic cancers, etc., it's mind boggling. By principle, it has to be unacceptable for the field.

This is the high-level overview of where we're at, and as you can hear, I'm not pleased. I hope that many people are not pleased by how these [shortages] developed, being taken by surprise, and suddenly realizing that there are major shortages [of carboplatin and cisplatin].

The initial guidelines that were developed did not seem to stand the test of even a week or two because the shortages developed so fast and ultimately were so impactful across the board. We can talk about some practical aspects of how institutions can try their best. However, the bottom line is that [these shortages] require a national emergency response to see how we can fix it. Unless we fix it, everything else is a little bit of lip service, as opposed to some true impact for patient care.

We have to fix it, and I'm pleased that after a couple of weeks of outcry from the field, ultimately, leadership has started to recognize that this is not something that guidelines [alone] can fix. There [has been] an FDA response, trying to fix the shortcomings in terms of the pipeline of these drugs, and, hopefully, there will be a national outline as to how we can prevent these [shortages] in the future.

What are some of the strategies being used to help navigate the cisplatin and carboplatin shortages?

In the meantime, we can help each other out in terms of some supply chain issues, where maybe an institution has a significant supply and they can distribute it to partner institutions, so that's very helpful. That happened to us. Suddenly, through some channels, we found some. Some suppliers recognized that the minority populations in the Bronx [may not] have the [same] voice that others might have, and it's important to elevate those voices so these patients do not get left behind. We had received a short supply, so each of us have been helping others out, which is terrific.

Within the short supply that each institution has, we have to set up teams managing the supply. What are the critical indications for the use of agent A vs agent B? Is there an indication that is so critically important that whatever supply [of a drug] we have, we have to protect it for use in those patients in curative settings? Let's say testicular cancer: How could we leave a young patient with testicular cancer behind, not offering [platinum chemotherapy] that has a very high chance of curing them [when there is] very little in terms of [agents that] could replace those drugs? Therefore, I believe highlighting indications that are of critical importance is [vital].

Outside of that, replacement strategies [could be an option]. For example, it turns out that carboplatin is in shorter supply than cisplatin for most institutions. Switching from carboplatin to cisplatin tends not to be the end of the world in many contexts. Those [agents] are almost but not always interchangeable. Let’s say instead of carboplatin, we use cisplatin. Well, that sounds great if you have a young patient who is quite healthy; however, if you have a frail, [older] patient, suddenly the cisplatin replacement can bring in some very significant toxicities. This [consideration of interchanging cisplatin for carboplatin] has to be context dependent. I really hope that outside of the guidelines, the patients’ needs and the clinicians’ voices at each institution will be heard as to the real needs.

Can we change regimens in terms of frequency? Well, sometimes it's not totally unreasonable to give a particular regimen a little bit less frequently, maybe shortening the number of doublet chemotherapy cycles if a patient doesn't have a very large burden of disease or switching to maintenance chemotherapy earlier with ongoing immunotherapy. If we're thinking about metastatic non–small cell lung cancer, and we have a threshold of a tumor proportion score of 50%, we might use immunotherapy vs chemoimmunotherapy. If there's such a shortage, that discussion might be tailored a little bit toward, “Well, maybe single-agent immunotherapy might need to be used a little bit more.” However, from there, suddenly the conversation can be a slippery slope, [where you are] using drugs that are not appropriate for an indication or just really don't make a ton of sense in the large scheme of things. Switching cheaper cisplatin over to nivolumab [Opdivo] plus ipilimumab [Yervoy] because of this national shortage might [be sustainable] for a few weeks, but we would bankrupt the health care system over the long term.

Again, if you have this conversation with colleagues for a while, you realize that the real solution cannot be [found] on this level. It has to be [made] on the national level to ultimately fix the supply. We can toy with these recommendations for a few weeks. However, there has to be a larger-level fix.

When you’re treating a patient who may be affected by the platinum shortage now or in the future, how would you handle those conversations about the current situation?

Ultimately, our patients are in a very difficult [situation] to begin with, facing a cancer diagnosis, which may be metastatic. They may be facing the challenge of issues of life expectancy and quality of life, [and then we] may be burdening them with the stress of having to decide between compromised treatment regimens. Minimizing that stress is very important. If you can avoid having patients make decisions in this context, it is for the best.

It's very important as a clinician to think through [the treatment plan]. Is there some appropriate replacement that is not such a major compromise? Can I support the regimen in a way so the stress of the decision doesn't have to [affect] the patient to the full extent? Maybe we can dampen the damage by carefully thinking it through, presenting options, and outlining the situation. [Assure them that you’ve] thought about it, discussed it with colleagues, and there are national guidelines. You can say, “I'm still taking care of you, and you can trust us.”

Carefully presenting [the options] in a thought-out and balanced way can minimize the stress, although stress will still be involved. No question. Some national guidelines recommend providing the help of counselors for patients. The updated guidelines suggest the same for clinicians, too.

What advice would you give to community oncologists to navigate the current chemotherapy shortages?

All of us are asking others how to manage a situation that we’re facing right now. Those discussions are ongoing [at] every single tumor board. I have asked my colleagues the same. Each of us has to recognize some of the new boundaries. We want to practice in an appropriate way. Given the shortcomings, [our goal is to] offer choices that are within the realm of what a prudent oncologist could support. This is where we can help each other out, just bouncing ideas off [each other].

What communication is required from the departments at Montefiore regarding the platinum shortage?

Cancer center leadership has put together a committee in a way to streamline the information flow between our research pharmacists, cancer center leadership, and our practice leadership as to what's available. What are we recommending for the next couple of weeks? What is the expectation long term? That's been something that has been happening maybe on a weekly or [bi-weekly] basis, depending on how the situation evolves.

In any institution, that makes sense, to create a centralized committee, but make sure that the committee communicates carefully and in a timely and transparent fashion. Make sure that it’s a universal approach.

Beyond that, though, we're all self-specialized in a way. A thoracic oncologist will have a hard time telling a gynecologic oncologist [about the] proper decision in a certain context. In head and neck cancer, usually we use cisplatin with radiation. There is some evidence that taxane-based treatment can do similarly well, so maybe in that context, a reasonable replacement can be found. Step by step, each disease [specialty] has to think about the very unique scenarios that they face and have a proper replacement or alternative strategy that can be delineated.