What PALOMA-3 Signals for Coverage, Access, and Care Delivery in NSCLC

Key Takeaways

• Subcutaneous amivantamab is noninferior to the IV formulation and offers major patient-centered benefits, including dramatically reduced time in the cancer center and fewer infusion reactions.
• Shorter administration times can significantly improve clinic workflow, patient throughput, and resource utilization, particularly for smaller oncology practices.
• While patient-reported outcomes and tolerability favor the subcutaneous formulation, long-term real-world data are still needed before considering home self-administration.

Narjust Florez, MD: Hi, everybody. My name is Dr Narjust Florez. I'm a thoracic medical oncologist at Dana-Farber Cancer Institute. I specialize in young patients with lung cancer and I have experienced using amivantamab for quite some time.

Can you provide a brief overview of the latest results of the PALOMA-3 study?

Dr Florez: PALOMA-3 is a study of amivantamab, which is a humanized monoclonal antibody that targets EGFR and MET. It compares the intravenous (IV) version, which was the first US Food and Drug Administration (FDA)-approved version of the drug, with the recently approved subcutaneous version of amivantamab, because it was just approved at the end of last year.

They're both in combination with a tyrosine kinase inhibitor, lazertinib. PALMOA-3 mostly is a non-inferior study that is comparing 2 formulations, amivantamab IV versus amivantamab subcutaneous.

From your perspective, how might subcutaneous amivantamab change clinic workflow, patient throughput, and overall care delivery in busy oncology practices?

Dr Florez: When we talk about amivantamab subcutaneous, we need to talk about it in 3 different ways. The first way will always and forever be our patients. How is amivantamab subcutaneous helping patients? The average infusion of amivantamab IV is 5 hours, that's the first day, and the patients need to come in the second day for another dose. It becomes weekly after that. [This is] 5 hours in infusion center versus the 4.8 minutes—5 minutes—that it takes for the subcutaneous administration.

The cancer center is not the number one location that patients like to go. We're no Mall of America. Patients want to come and go as fast as they can. Cancer centers can be challenging. They're usually very sad. So, the first benefit is less time in the cancer center. A lot of patients have to take time off work to get treatment. If you have to take 1 hour off work, that is less lost wages compared to 5 hours and the subsequent day.

In addition to that, amivantamab subcutaneous has significantly less infusion reactions. There's a high rate of infusion reactions with amivantamab IV, around 60% or higher. These reactions can be very uncomfortable. We're still on the number one reason: patients. They can get very red, like a tomato. They can have shortness of breath, back pain, tachycardia, and I prepare my patients for the infusion reaction, but being prepared for the infusion reaction generates anxiety before the reaction.

With the subcutaneous [formulation], we don't eliminate, but we significantly reduce the rates of infusion reactions. It reduces the rates of, for example, anxiety that the patient would have. That is very patient-oriented: less reactions, less time in the cancer center.

Number two is workflow. Currently, in the most updated American Cancer Society (ACS) report on the status of cancer—an epidemiology report that we all wait for, it's released early in the year—it has shown that over 70% of patients with cancer are living past 5 years. That means our patient load has significantly increased, and our cancer centers do not expand as fast as our survivors do. It is becoming more and more challenging to get a chemotherapy chair.

At Dana-Farber, we have hundreds of chemotherapy chairs. In one of my clinics, on one floor only, I think we have over 115 chairs. But for small practices that have 8, 12, or 20 chairs, it is very hard to reserve one entire chemotherapy chair for the amivantamab patient who will be there for 5 hours. To be clear, these are 5 hours if everything goes well, and then they have to reserve the chair for the next day.

By having the subcutaneous formulation, we decrease the amount of chair time and open the door to patients who need treatment. Again, back to number one: patients, always. The more chairs we have, the faster patients can get into treatment. That's what I think, when it comes to the workflow of the clinic, we significantly improve.

I had a patient who started amivantamab IV because subcutaneous is not available in my clinic yet, and I can't tell you the amount of emails it took to plan that and the amount of work. There's a lot of human power that goes into scheduling IV amivantamab. That is the clinical benefit.

Third, we hope that we help our very financially challenged health care system, because that equals money. The less resources we need, the less we take from a health care system that continues to bleed in the United States and globally. These 3 things regarding subcutaneous amivantamab not only apply to the United States, they apply globally. That's what is important.

However, we need to remember that subcutaneous amivantamab in PALOMA-3 lowered the rates of infusion reactions but did not lower the rates of other side effects. That did not happen. So, the skincare still needs to continue. I would ask everybody to refer to the article we published last year in The Oncologist, which is a guide on how to manage amivantamab side effects. It's a practical guide with recommendations. We even went to dermatologists. Subcutaneous amivantamab does not decrease the skin reactions, the liver dysfunction, and the swelling that happens with the drug.

Patient-reported outcomes strongly favored the SC formulation in terms of convenience, time burden, and satisfaction. In a post-osimertinib population where treatment fatigue is common, how important are these patient-experience factors in sustaining adherence and optimizing outcomes?

Dr Florez: When we look at PALOMA-3, we see an improvement in survival with the subcutaneous administration. The pharmacokinetics show that the subcutaneous and the intravenous are even, so why are people in the subcutaneous living longer?

One hypothesis to this is that patients are more likely to tolerate the drug. They're more likely to stay on the drug because the main challenge with amivantamab is not that the drug doesn't work, it's that the drug is toxic. Changing the formulation allows patients to tolerate treatment better, stay on the drug better, and subsequently improve survival. I would prefer to get a shot in my belly than be there waiting to have a reaction.

In addition to that, with the introduction of GLP-1s, people are way more comfortable now with subcutaneous injections. General people, not doctors. That's something to take into account.

Another thing I think regarding patient-reported outcomes that makes a difference is that they have more time to take care of the side effects if they are not in the cancer center. The regimen, which is the COCOON regimen, to prevent some of the adverse events of amivantamab or help them is time consuming. If you spend less time in the cancer center getting an infusion, you have more time to put lotion all over yourself, which is what is needed.

How do these findings align with the unmet needs observed in the coverage landscape for medications related to NSCLC?

Dr Florez: There's still a lot of work to do. Amivantamab is a first-generation drug that we need to improve. The MET inhibition is good for patients who have resistance mechanisms, but there are patients that don't. It's still not a very specific inhibitor, like other inhibitors we have in this space.

Why is PALOMA-3 great for administration? I think the future of amivantamab is to make a molecule that will target EGFR better and will prevent those off-pathway side effects that are very challenging, like swelling. I have patients who have swelling in their eye lips and swelling in their vaginal lips.

Having an agent that evolves for amivantamab is the beginning of the road, not the end, to having another monoclonal humanized antibody that will help us be more on target to EGFR and avoid the side effects that are off target.

What is the primary message you aim for the audience to take away from this interview?

Dr Florez: A message to patients is that while the subcutaneous administration has been approved, I do not think we're ready for patients to self-administer at home. We need more time off the market. In clinical trials, all the settings are controlled. Everything is controlled; everything is supervised. There are a million safety checks. We need to know how amivantamab subcutaneous or under the skin does in the real-world setting for a few years before patients will do it at home.

I'm saying this because patients ask me, "Oh, so can I do it myself?" We're not there yet. We need to know how the drug will perform outside of the clinical trial, in reality, before patients are able to do it at home.