Anna C. Pavlick, DO
For patients who have higher-risk melanoma, including those who are in stages IIb to IIIc or resected stage IV disease, the primary concern is that they will experience disease recurrence or relapse. The best option for these patients is to receive effective adjuvant therapy, but there are challenges in deciding which agent is best for this patient population.
In a recent interview, Anna C. Pavlick, DO, associate professor of hematology and medical oncology and medical director of the Clinical Trials Office at the Perlmutter Cancer Center at NYU Langone Medical Center, discussed adjuvant therapy for patients with high-risk melanoma.
“I reviewed the historical data looking at interferon as the only adjuvant we had for many years, and now we have the checkpoint inhibitor ipilimumab (Yervoy) that has been approved to be given in the adjuvant setting for stage III patients,” Pavlick said in an interview during the meeting.
Pavlick emphasized the importance of clinical trials, adding that increased participation in clinical trials will bring effective change in what treating physicians can offer patients, as well as coming to a better understanding on what are the best options to treat high-risk melanoma.
Oncology Nursing News: You lectured on the utility of interferon in the adjuvant setting for melanoma treatment. How often is this therapy used today?
: There are very isolated groups throughout the United States that believe that data. If looking at the East coast and West coast regions of the country, we are “non-interferon believers.” However, the middle of the country is still using interferon. If you talk to an oncologist on the East coast, we would say that we don’t really use it. I would never say “never;” however, I haven’t administered it to patients in the past 3 to 5 years. I would rather put patients on a clinical trial and look for something much more promising with less toxicity—with the hope that it will impact their survival—when I know that interferon with its toxicity is not going to impact their survival.
What trends are we seeing in ongoing clinical trials, and what types of patients that would be best for each type of trial?
Depending upon a patient’s stage of disease, the earlier-stage high-risk patients—like those with IIb, IIc, and IIIa disease—are those who may be interested in a vaccine trial. We look at different peptides that may be able to immunize patients to decrease their risk of recurrence. We don’t know if a certain peptide is going to benefit the patients. However, most vaccines have very minimal toxicities, they’re tolerable, and patients can come in and receive the vaccine and then go to work afterward since they are not sick. We are hoping that we are able to find one that may be able to help them.
For patients that have high-risk disease—such as IIIb, IIIc, and resected stage IV disease—we are looking at the usefulness of using checkpoint inhibitors in an earlier setting rather than waiting for patients to develop metastatic disease. There are plenty of clinical trials that are looking at single-agent PD-1 inhibitors, comparing interferon or ipilimumab with a PD-1 inhibitor, or there are combination trials looking at what we call “flip doses.”
The way we give combination immunotherapy is usually 3 mg/kg of ipilimumab with 1 mg/kg of nivolumab (Opdivo) during a patient’s induction. What we have done is flipped the doses, so we are giving 1 mg/kg of ipilimumab and 3 mg/kg of nivolumab. The toxic drug in that combination is the ipilimumab, but we also think it’s really important to stimulate those T cells to generate a better immune response. We want the patients to get ipilimumab, but we don’t want them to get the related toxicity. Our hope is that by flipping these doses, we will be able to get the same great responses with the standard doses but with a lot less toxicity.
What determines how long you administer adjuvant therapy to your patients?
If the patients are going to participate in a research study, the length of treatment is dictated in the protocol. If you’re participating in a vaccine study, some vaccine studies run 6 months, and some run a year. Most adjuvant studies don’t run more than 1 year, even with the inhibitors it’s the same thing. The trial studying ipilimumab and interferon versus pembrolizumab has treatment over 1 year. Then, you watch.
Were there any recent adjuvant data in melanoma presented at the 2017 ASCO Annual Meeting?
What was presented at ASCO that we all found intriguing was a study comparing 3 mg/kg to 10 mg/kg of ipilimumab, because the 10 mg/kg dose is what is approved for the adjuvant setting, but the 3 mg/kg dose is what is approved for patients with metastatic disease. We know that 10 mg/kg gives a lot of toxicity—more than the 3 mg/kg—and so we put those 2 doses in a head-to-head comparison.
We saw that the rate of relapse-free survival for the 2 doses is actually the same, but this is a very early look at the data. We don’t have a comparison for survival we can use as evidence that if we give a patient the 3 mg/kg dose, their survival is going to be as good as the 10 mg/kg dose. We can tell patients the toxicity is a little bit better, but what really matters most is survival, so if we can provide the same survival benefit at a lower dose, and with less toxicity, that’s certainly what we want to do.
What do you hope that community oncologists take away from your presentation, as well as attending the State of the Science SummitTM?
I hope that the community walked away with the understanding that melanoma is advancing very quickly. It’s not the lethal disease that it used to be—even 5 years ago—as we develop newer agents and bring them to the forefront in higher-risk patients. We are hoping to be able to impact these patients so they never get metastatic disease.
The most important thing is they consider putting patients on clinical trials so we can get this data, and we can know what the right drug is or what the right treatment is for patients in the adjuvant setting. If we just “fly by the seat of our pants” and just routinely give patients 3 mg/kg of ipilimumab, how do we know what effect that’s giving the patient? Let’s get the data, let’s do it right, and let’s keep putting patients on trials so we can move the field forward in a very positive way.