Ipilimumab Conveys Long-Term Survival Benefit in Pooled Analysis of Metastatic Melanoma Patients


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In the treatment of metastatic or locally advanced unresectable melanoma, the anti–CTLA-4 monoclonal antibody ipilimumab (Yervoy) conveys long-term survival benefits, with some patients alive out to 10 years, according to the largest survival analysis of the immunomodulating agent, presented at the 2013 European Cancer Congress by Stephen F. Hodi, MD, Director of the Melanoma Center at Dana-Farber Cancer Institute, Boston.1

“The observed ipilimumab overall survival curve demonstrated greater durability of survival, relative to historical data in the pre-BRAF inhibitor era,” he said. “This analysis adds to the evidence supporting a durable, long-term survival effect of ipilimumab in patients with advanced melanoma.”

Study Details

The pooled analysis included 1,861 patients from 12 prospective and retrospective trials, and an additional 2,985 patients who were treated with ipilimumab outside of a clinical trial in the expanded access program. The findings are the most precise estimate yet of the benefit of ipili-
mumab, Dr. Hodi said.

The analysis of the 1,861 patients in trial registries found median overall survival to be 11.4 months, with 254 patients (22%) alive 3 years after initiating treatment with ipilimumab. Median overall survival for the whole population, including the 2,985 patients in the expanded access program, was 9.5 months, with 3-year survival in 21% of patients. Dr. Hodi attributed the slightly shorter survival time in this group to limited data and to the possibility that this was a sicker population.

In both groups, the benefit of the drug appeared to plateau after about 3 years. Beyond 7 years, no deaths were reported, and median 7-year overall survival was 17%. The longest recorded survival was 9.9 years.

This survival plateau was observed regardless of dose (3 or 10 mg/kg), previous treatment, or the continued use of ipilimumab as maintenance, he said.

Treatment-naive patients had a median overall survival of 13.5 months, vs 10.7 months for previously treated patients, most of whom did not receive a BRAF inhibitor. Three-year survival rates were 26% and 20%, respectively.

“Around the inflexion point of 3 years, there seems to be a flattening of the tail of the curve,” Dr. Hodi noted. “Going forward up to 10 years, with lots of censoring, we see a group of patients maintaining a survival advantage long term.”

Metastatic Melanoma as Chronic Disease?

Alexander Eggermont, MD, General Director of the Institut Gustave Roussy Comprehensive Cancer Center in France, who is Past President of the European Cancer Organization, commented on the findings. “This pooled analysis clearly demonstrates that ipilimumab can lead to long-lasting tumor control in metastatic melanoma patients. With a response rate of only 10% to 15%, one can achieve more than 3 to 10 years of survival in 17% to 25% of patients who have received only a few doses of ipilimumab. Thus, patients apparently can keep residual tumors under control for a long time when the immune system is properly ‘reset,’ and the concept of ‘clinical cures’ becomes a reality.”

Dr. Eggermont and Dr. Hodi agreed that when novel antibodies targeting the programmed death 1 protein and its ligand (anti–PD-1/PD-L1) become available, metastatic melanoma could become a chronic illness and potentially “curable” in some patients.

“A few years ago, I could never imagine using the ‘C’ word, or see patients living long term,” Dr. Hodi commented. “What we are showing is a great paradigm shift. At least we are turning this disease into a chronic illness. Possibly, in a subset [of patients], we are beginning to consider that this could be a cure. I remain optimistically conservative on that point, but we are headed in the right direction.” ■

Disclosure: Dr. Eggermont participates in scientific advisory boards for Bristol-Myers Squibb, MSD, GlaxoSmithKline, and MedImmune.

Reference

1. Schadendorf D, Hodi FS, Robert C, et al: Pooled analysis of long-term survival data from phase II and phase III trials of ipilimumab in metastatic or locally advanced, unresectable melanoma. 2013 European Cancer Congress. Abstract LBA24. Presented September 28, 2013.



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