Dr. Balazs Halmos discusses the significance of the approval of subcutaneous Opdivo and what this treatment formulation means for those with solid tumors.
The Dec. 27, 2024, Food and Drug Administration (FDA)
This regulatory approval represents a new, safe and effective way to administer Opdivo for patients with melanoma, renal cell carcinoma, head and neck squamous cell carcinoma, non-small cell lung cancer, colorectal cancer, urothelial carcinoma, esophageal carcinoma, hepatocellular carcinoma, gastroesophageal junction cancer, gastric cancer and esophageal adenocarcinoma,
In an interview with CURE®, Dr. Balazs Halmos stated, “Now, we can allow some patients to receive [treatment] more flexibly, more conveniently, while saving time, maintaining quality of life and allowing patients to spend as much time away from the infusion center and the physician's office as possible.”
In the interview, Halmos elaborated on the significance of the FDA approval of subcutaneous Opdivo for eligible patients, as well as expanded on what this new treatment formulation can mean for patients.
Halmos currently is a professor in the Department of Oncology (Medical Oncology) and in the Department of Medicine (Oncology & Hematology) at the Albert Einstein College of Medicine, as well as an Associate Director of Clinical Science at the Montefiore Einstein Comprehensive Cancer Center, located in New York City.
Intravenous (IV): when a needle is inserted into a vein to administer fluids or medications directly into the bloodstream.
Subcutaneous: beneath the skin.
The Food and Drug Administration (FDA): a federal agency that protects the public's health.
Hamos: Any FDA approvals we take very seriously, as it allows us, as oncologists, to be able to use new products for new indications, or sometimes old products in different ways. This is one of those medicines that we've been very successfully using for a decade in many different cancer types. This medicine, Opdivo, is based on a discovery that led to a Nobel Prize and is one of those immune checkpoint inhibitors that can re-energize the immune system's ability to fight different cancers as foreign elements in our bodies. This is a very successful drug. We use it frequently in the management of different types of lung, skin and gynecological cancers.
Traditionally, this medicine has to be given through the IV [intravenous], and it's nice to see a new wave of improving the quality of care for patients by allowing some of these medicines to be given subcutaneously, meaning under the skin. Of course [this approval of subcutaneous Opdivo is] still an injection, but it's an injection that can be quicker, more convenient, and for some patients, potentially less painful. It also allows for a lot of time savings in the physician's offices. [For example], maybe there's not a need to wait for an infusion chair. From that standpoint, it's not a major advance for the field, but it could be a significant advancement for any given patient who needs some of these treatments. That's what this approval is about.
The FDA always takes this job very seriously and requires the company — in this case, Bristol Myers Squibb — to conduct a very large, randomized phase 3 pivotal study to be certain that we're not short changing patients, that we're not giving medicines that might not be as effective as the IV version. This was a large,
The patients received the medicine and then the study groups were compared, [evaluating if] the same level of the medicine in the bloodstream [was reached]. That was the primary end point of this study; it's a very important measurement to ensure that the subcutaneous medicine gets into the bloodstream exactly the same way, or potentially even better, than with the more conventional IV version. It also looked at a clinical end point where we see shrinkage of the kidney cancers in a similar fashion, at a similar rate as with the IV version.
In the study of over 400 patients, that's exactly what we saw, that the primary goal was reached. The medicine is able to get into the bloodstream just as well. In fact, if you look at the numbers, [it was] potentially better than the IV version. Now, different doses were given intravenously versus subcutaneously. Either way, the approved dosage of this medicine subcutaneously matched or was potentially superior to the approved version IV, as to getting a concentration in the bloodstream. It also allowed as many patients to respond to the medicine, with 24% of the patients having shrinkage of the tumor in the subcutaneous group — the under the skin group — versus 18% in the conventional IV group.
[This reinforces] that yes, the medicine behaves as it should in the human body, even though it's given under the skin, and yes, the cancers can benefit similarly to the IV version.
Currently, the conventional version is given through an IV, so an IV has to be placed; generally speaking, this is typically given in an infusion center. So many times, the patient needs to be seen in the office by a doctor and then go to an infusion center; maybe it's in the same building but maybe it is not, and [they then] have to wait for an infusion chair, get an IV placed, and get the medicine that way. This new version allows the injection under the skin to be given in a larger variety of settings. Maybe it can be in the doctor's office. Maybe in the future, it can be in patients’ homes as well. It allows flexibility and also saves some time.
There's no need to wait for the infusion chair, no need to wait for an IV to be placed [with this new indication]. That being said, it doesn't help everyone to save a lot of time, as many times these medicines are given in combination. If, in the combination, the rest of the medicines have to be given in the IV, there's not much of a reason or point to get the subcutaneous injection, as opposed to receiving it in the IV. Therefore, it depends on the context.
The FDA did not approve this medicine to be given in combination with another immunotherapy drug called Yervoy [ipilimumab]. It is important to remember that it will not be every single patient where the subcutaneous version can be used, but in many, many settings, it could potentially yield savings for patients.
This is not the first medicine that we have seen go from an IV formulation to both an IV and subcutaneous formulation, though the adoption varies. Some physician practices do not see that much of an advantage, and may stay with the IV version, but it's nice to have the flexibility. For example, if a patient requires this medicine once a month, to be able to receive it subcutaneously allows that flexibility and potentially time to be saved.
I do foresee many practices adopting it as one option, and patients can potentially decide themselves if they favor this versus the more conventional approach.
Firstly, the patient would need to have an indication to receive the medicine Opdivo. The clinical study was focused on patients with kidney cancer, but the FDA took a broader view, saying that if it worked just as well in the IV formulation for kidney cancer, I'm willing to sign off on it for other cancer types as well. Patients with any cancer type where Opdivo is recommended can be considered for the subcutaneous version. That being said, if there's an IV combination involved, it doesn't make sense, as it's currently not approved yet.
The ideal context is when Opdivo is given on its own. In that case, subcutaneous and IV both will be options. Patients, with their physician’s help, can potentially choose which one would they favor for the best quality of life and outcomes in terms of cancer control.
Additionally, the side effect profile of the IV versus the subcutaneous versions seem to be practically identical, with very little skin reactions at the injection site noted in patients who received the subcutaneous version, and those tended to be very mild.
We're just all thrilled that there's a broader and broader range of patients that can benefit from novel medicines. Whether those are targeted medicines or immunotherapies, the range is getting wider and wider. That's a nice goal and advance to be seen.
Transcript was edited for clarity and conciseness.
For more news on cancer updates, research and education,
