Five-Year Analysis Shows Ipilimumab More Than Doubles OS in Advanced Melanoma

Michael A. Postow, MD

The first analysis of long-term survival of ipilimumab for patients with advanced melanoma found a 5-year survival rate of 18.2% for patients treated with ipilimumab (Yervoy) plus dacarbazine versus 8.8% for patients treated with dacarbazine alone (P = .002), according to results recently published in the Journal of Clinical Oncology.

While these findings were somewhat expected given the favorable outcomes of ipilimumab shown in prior studies, they are still significant, according to Michael Postow, MD, a medical oncologist specializing in melanoma at Memorial Sloan Kettering Cancer Center, one of the locations involved in the analysis.

“We knew that ipilimumab plus dacarbazine had a better benefit than dacarbazine alone, but we didn’t know how long that survival benefit lasted,” said Postow in an interview with OncLive. “Now we can say the benefit lasts at least 5 years. The purpose of this study really was for the first time to report this long survival in the context of a randomized study and it clearly showed that the people that get ipilimumab have more than twice the chance of living longer than people that just get dacarbazine alone.”

The analysis involved a review of data from the CA184-024 trial, which randomized patients with advanced melanoma in a 1:1 ratio to receive ipilimumab at 10 mg/kg plus dacarbazine at 850 mg/m² (n = 250) or placebo plus dacarbazine at the same dose (n = 252) at weeks 1, 4, 7, and 10, followed by dacarbazine alone every 3 weeks through week 22. Eligible patients could receive maintenance ipilimumab or placebo every 12 weeks beginning at week 24.

For the overall study population, the median survival follow-up for the ipilimumab and control arms was 11.0 and 8.9 months, respectively. The updated median overall survival (OS) was 11.2 months in the ipilimumab plus dacarbazine group and 9.1 months in the dacarbazine-alone group.

At ≥5 years’ follow-up, there were 40 patients alive in the ipilimumab arm, and 20 patients in the dacarbazine-alone group. Most of these patients had an ECOG performance status of 0. The median age was 57.5 and 61.0 years in the ipilimumab and the control arms, respectively.

As previously noted, the 5-year OS rate with the ipilimumab combination was 18.2% (95% CI, 13.6%-23.4%) compared with 8.8% (95% CI, 5.7%-12.8%) for dacarbazine alone. The authors noted that the survival curve for ipilimumab began to plateau at about 3 years.

A complete response was achieved by 7.5% of patients in the ipilimumab arm at 5 years, with 42.5% of patients achieving a partial response, for an objective response rate of 50%. In the placebo arm, no patient achieved a complete response, but a partial response was observed in 35% of patients. Stable disease was achieved by 27.5% and 40% of patients in the ipilimumab and control arms, respectively. The proportion of patients with disease progression was similar between the two groups at 17.5% versus 15.0%.

According to the authors, grade 3/4 immune-related adverse events (irAEs) observed with ipilimumab at 5 years’ follow-up all impacted the skin and included rash, vitiligo, and pruritus. Low-grade irAEs that affected the GI tract, liver, and endocrine system were also reported.

Since its approval in 2011, ipilimumab has had a huge impact on the treatment paradigm for melanoma, said Postow. But more research is needed to fully understand what the results of this trial mean. In the United States ipilimumab is typically used alone instead of in combination with dacarbazine, as was the case in the study.

“Because this study did not include an ipilimumab-alone arm, we don’t know if dacarbazine added to the effects of ipilimumab or did nothing,” said Postow. “So it remains unknown if dacarbazine plus ipilimumab is better than ipilimumab alone. I think it would be an interesting question to answer.”

Longer-term follow-up on patients in the ipilimumab arm is also necessary to fully understand the impact of ipilimumab. Postow believes that the drug will continue to show improved survival over time, but he would like to see studies confirming that assumption.

“Right now it does seem like the long-term benefit is absolutely clear for ipilimumab, doubling overall survival after 5-years,” Postow said. “But if that doubling doesn’t persist for another 5 years when we look at this again, that is concerning.”

Reference

Maio M, Grob JJ, Aamdal S, et al. Five-year survival rates for treatment-naive patients with advanced melanoma who received ipilimumab plus dacarbazine in a phase III trial [published online February 23, 2015]. J Clin Oncol. doi:10.1200/JCO.2014.56.6018.