New Long-term Data 'Clearly Favor' Combination Ipilimumab/Nivolumab in Melanoma

This transcript has been edited for clarity.

I'm Dr Jeffrey Weber, a medical oncologist at the Laura and Isaac Perlmutter Cancer Center at NYU Langone Health here in New York City. I would like to report to you today on several abstracts presented at the recent ASCO meeting that was held virtually. Both were long-term updates of important, large trials that were conducted over the past couple of years.

The most important one, in my view, was the 6.5-year, very long–term follow-up on the CheckMate 067 trial, presented by Dr Jedd Wolchok from Memorial Sloan Kettering. This was a large randomized trial of ipilimumab/nivolumab (IPI/NIVO) vs NIVO alone vs IPI alone. The response rate continues to be impressive for the IPI/NIVO arm at 58%, with a 45% response rate for the arm that received NIVO alone, and of course much less, 19%, for IPI alone.

Progression-free survival at 6.5 years of follow-up was 34% for the combo and 29% for NIVO alone. The median overall survival was 72 months for IPI/NIVO, which is very impressive, vs a 36.9 months for NIVO alone and 19.9 months for IPI alone. There is clear superiority all the way along that curve, starting at about a year of follow-up.

The melanoma-specific survival, which was a very interesting post-hoc analysis that we'd never seen, was 56% vs 48% for the combo vs NIVO alone, respectively, clearly favoring the combo. If you look at the patients who had a CR in either arm, whether it be IPI/NIVO or NIVO, it's 88% or 89% alive at 6.5 years vs only something like 66% for those who got IPI alone, again favoring the combination in every way, shape, or form.

If you look at the BRAF status, mutated vs wild-type, in terms of overall survival and progression-free survival, there was a minimal change, slightly favoring the BRAF-mutated population. That's probably because of the availability of subsequent BRAF/MEK therapy for the mutated population.

Interestingly, as we've seen with PD-1 alone, with liver metastases, you definitely do better. It's something like 56% 5-year survival vs 42% 5-year survival. It continues very similarly at 6.5 years. You don't want to have liver metastases if you get treated with immunotherapy.

The treatment-free interval is vastly superior for the combination vs PD-1 alone. If you look at those patients still alive, 77% of them are free of further treatment on the combo arm vs 69% for NIVO alone and only 43% for IPI alone. Whichever way you cut it, there is clear-cut evidence of benefit for combination IPI/NIVO at 6.5 years of follow-up compared with NIVO alone or IPI alone.

The next long-term follow-up study was the 5-year follow-up on the Australian ABC Study, which was a study of patients with brain metastases who received either IPI/NIVO or NIVO alone with a small cohort of symptomatic patients or leptomeningeal patients. The nice thing about this study is that you could have multiple brain metastases and the patients were not treated with stereotactic radiosurgery.

There were 35 patients in the IPI/NIVO arm and 25 in the group that got NIVO alone, and only 16 in the NIVO group that had either symptomatic disease on steroids or leptomeningeal disease. If you look at the intracranial response rate for the combo, the updated rate was 51% vs only 20% for NIVO alone. If you look at the treatment-naive patients — patients could have had prior treatment on this trial systemically — the intracranial response was 59% in the previously untreated patients. Again, these are very impressive data.

The extracranial best overall response rate was 57% for the combo, as you would expect for IPI/NIVO alone at the standard doses, and only 29% for NIVO alone. There were significant changes in intracranial progression-free survival. It doubled from 2.5 to 5.4 months. If you look at the survival of those who had a complete response intracranially at 5 years, 92% had not progressed. Again, those are very impressive data.

If you look at the rate of radionecrosis, those who progressed intracranially and then get stereotactic radiosurgery, it's really very small — in the range of 10%-20%. The overall survival was 51% at 5 years for the combo arm vs 34% for the NIVO arm alone. If patients had symptoms, overall survival was terrible at 13%.

Again, very nice data clearly show that your intracranial and extracranial response rates with IPI/NIVO beat NIVO alone, as you would expect. Long-term survival clearly beats single-agent drug alone. If you have symptoms or leptomeningeal disease, 5-year survival is pretty dismal.

This is Dr Jeffrey Weber. Please do feel free to call in with comments and questions. Thank you for your attention.

Jeffrey Weber, MD, PhD, is deputy director of the Laura and Isaac Perlmutter Cancer Center at NYU Langone Medical Center and co-director of its Melanoma Research Program. His research, which has been continuously funded by the NCI for more than 20 years, focuses on experimental therapeutics and drug development, particularly in immunotherapy.

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