Ipilimumab ‘Promising’ for Stage III Melanoma

Immunotherapy results reported for patients with stage III and IV melanoma

medwireNews: Final analysis of a phase III study suggests that adjuvant treatment with ipilimumab, a Monoclonal antibody against a cytotoxic T lymphocyte Receptor, reduces the risk of recurrent melanoma in patients with high-risk stage III disease.

American Society of Clinical Oncology (ASCO) expert Steven O’Day described the results as “promising” in a press release from the ASCO annual meeting, held in Chicago, Illinois, USA.

“The magnitude of the clinical benefit, the side effects, and the dosing schedule warrant further follow up and additional comparative studies with interferon, which are ongoing”, he added.

Ipilimumab given to 475 patients was associated with a 3-year recurrence-free survival rate of 46.5% compared with 34.8% for the 476 patients given placebo, with a 33% and 17% reduction in the likelihood of recurrence in patients with microscopic and macroscopic lymph node metastases, respectively.

The drug, which is currently licenced in Europe as a second-line treatment for metastatic melanoma, was given every 3 weeks for four doses followed by 3-monthly treatments for up to 3 years.

“This trial with ipilimumab is the first to show we may be able to give these new drugs earlier in the course of disease, where they can do more good and potentially cure more patients”, commented lead author Alexander Eggermont, from the Cancer Institute Gustave Roussy in Villejuif, France, and team.

However, he noted that the side effects were substantial, with five treatment-related deaths and over half of patients discontinuing ipilimumab because of colitis and other symptoms.

ASCO also saw reports from other immunotherapy trials for melanoma. Phase I results for ipilimumab in combination with nivolumab, a monoclonal antibody against the activated T cell protein PD-1, were reported for 53 patients with inoperable stage III or IV melanoma.

In all, 41% of patients responded to treatment consisting of ipilimumab plus nivolumab every 3 weeks for four cycles followed by nivolumab every 3 weeks for four cycles. Patients without progression then were offered combined therapy again every 12 weeks for eight cycles.

Median survival reported at the time of analysis was 39.7 months, with 1-year and 2-year survival rates of 85% and 79%, respectively.

“While we’re encouraged by what we’re seeing with the use of these two drugs together, this trial was small, so a randomized phase III trial will be important to validate our initial results”, commented lead author Mario Sznol, from Yale School of Medicine in New Haven, Connecticut, USA.

Phase I results for a second monoclonal antibody against PD-1, MK-3475, were also reported for 411 patients with advanced melanoma and metastases to the skin, lungs or other major organs.

The team, led by Antoni Ribas, from the University of California in Los Angeles, USA, says that 34% of patients achieved a tumour response, including 28% of patients with disease progression after ipilimumab and 40% of patients who had not been treated with ipilimumab.

Similarly, 1-year overall survival was reported as 69% of patients, 65% for patients previously given ipilimumab and 74% for ipilimumab-naïve individuals, with response ongoing in 88% of patients after a median follow-up of 1 year.

“We were excited to see that MK-3475 was effective in previously untreated patients as well as in those who had multiple prior therapies, including ipilimumab”, Antoni Ribas commented in a press release.

And although 8% of patients had grade 3 or 4 adverse events, just 4% of patients discontinued treatment for this reason.

Noting the low toxicity, ASCO expert Steven O’Day commented on the findings: “Anti PD-1 as a single agent is a major breakthrough and improves on the initial success of ipilimumab in metastatic melanoma.”


Abstract LBA9008. American Society of Clinical Oncology 50th Annual Meeting; Chicago, Illinois, USA: 30 May to 3 June 2014.

Abstract LBA9003. American Society of Clinical Oncology 50th Annual Meeting; Chicago, Illinois, USA: 30 May to 3 June 2014.

Abstract LBA9000. American Society of Clinical Oncology 50th Annual Meeting; Chicago, Illinois, USA: 30 May to 3 June 2014.

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