Nivolumab/Ipilimumab Shows More Promising Results in Patients with Melanoma

Findings from the phase III CheckMate-067 trial, which investigated the combination of nivolumab (Opdivo) and ipilimumab (Yervoy) to treat patients with advanced melanoma, showed potential biomarkers in patients who achieved a complete response at 5 years, according to Georgina V. Long, PhD, BSc, MBBS, FRACP.

Long, co-medical director of Melanoma Institute Australia (MIA), chair of Melanoma Medical Oncology and Translational Research at MIA and Royal North Shore Hospital, University of Sydney, presented these findings at the 16th International Congress of the Society for Melanoma Research (SMR). She discussed how the patients were alive at 5 years were an enriched population more likely to achieve a complete response.

Long also had the chance to sit down with OncLive, a sister publication to Oncology Nursing News, and discuss the findings of the study along with toxicities that oncology professionals should look out for during the course of the treatment.

OncLive: What are the current treatment options for patients with advanced melanoma?

Long: For people with advanced melanoma, the approved drugs in many countries around the world include 2 types of treatments, immunotherapy and targeted therapy. The targeted therapies are BRAF plus MEK-inhibitors for those who carry the BRAF mutation in their tumor — that’s about 40% of all advanced melanoma patients. The immunotherapies work in all patients whether they're BRAF wildtype or BRAF mutant.

Now I should qualify that the immunotherapies don't work in all patients, but they're potentially available for all patients. The immunotherapies include checkpoint inhibitors, the CTLA-4 and anti-CTLA4 with ipilimumab, and anti-PD1 with either nivolumab or pembrolizumab. We also have the combination of ipilimumab with nivolumab as an option for patients.

What were some of the findings from studying this combination?

When we looked at the descriptive analysis of subgroups, those alive at 5 years are an enriched population, more likely to have had a complete response, are more likely to have had a lower LDH or a normal LDH baseline and are more likely to have a lower numbers of metastatic sites. That's a marker of lower volume of disease, and that's what we see across all the drug treatments we now use in melanoma.

Patients who get a complete response have low volume of disease in a normal LDH baseline, and tend to do better on all our drugs. And indeed, we see this with both the combination of nivolumab plus ipilimumab and nivolumab alone.

So that was one finding from the study — 5 years survivors are enhanced with patients like that. It doesn't mean that if you have poor prognostic features you won't be alive at 5 years. You can, it's just enriched for those sorts of patients. The other thing we looked at in the study was how well do people do based on their response, their resist response. So, we found that for patients who had a complete response, 80% of them remained in complete response at 5 years, and that was also the same for nivolumab. Eighty percent was nivolumab combined with ipilimumab 79% of those who had a complete response on nivolumab had not progressed by 5 years.

What is the toxicity profile of this combination?

We do see toxicity with the combination compared with the monotherapy nivolumab. Nivolumab combined with ipilimumab we see a rate of grade 3-4 treatment related adverse events just under 60%. Many of those are reversible with corticosteroids.

The ones that are not reversible tend to be the endocrinopathies, that's thyroid or hypopituitary and rarely type-1 diabetes, but they can be managed with replacement drugs. So, for example, replacement thyroid hormone, and replacement corticosteroids and for type-1 diabetes insulin. Although that can be an impact on people's quality of life.

So, it's certainly more toxic, but we see fewer grade 3 for a treatment related adverse events with nivolumab alone. Again, a similar pattern though, I mean, we're talking less than 20% grade 3-4 but a similar pattern, in that, most of the side effects are reversible with cessation of treatment, sometimes you need steroids to reverse them, but the endocrinopathies are not reversible, but you are able to replace the hormone.