Adjuvant ipilimumab improved RFS in high-risk, stage III melanoma

Source: www.healio.com/hematology-oncology, June 2014

Adjuvant ipilimumab significantly improved RFS compared with placebo among patients with resected stage III melanoma who were at high risk for recurrence, according to the final analysis of a phase 3 study presented at the ASCO Annual Meeting.

“Although there are approved adjuvant therapies, they are still to be improved, and this is clearly an unmet need,” researcher Alexander Eggermont, MD, PhD, director general of the Gustave Roussy Cancer Campus Grand Paris in France, said during a press conference. “Ipilimumab is the first drug approved for metastatic melanoma, based on a proven impact on OS. This is the first trial ever with a drug that had an improvement in OS in metastatic melanoma.”

 

The analysis included 951 patients with stage IIIA (20%), IIIB (44%) or IIIC (36%) disease. Forty-two percent of patients had ulcerated primary disease, and 58% had macroscopic lymph node involvement.

Eggermont and colleagues randomly assigned 475 patients to receive 10 mg/kg ipilimumab (Yervoy, Bristol-Myers Squibb) every 3 weeks for four doses, followed by doses every 3 months up to 3 years. The other 476 patients received placebo.

Patients were stratified by disease stage.

After a median follow-up of 2.7 years, 294 RFS events occurred in the placebo arm and 234 occurred in the ipilimumab arm.

Researchers reported significantly longer median RFS in the ipilimumab arm (26.1 months vs. 17.1 months; HR=0.75; 95% CI, 0.64-0.9).

More patients assigned ipilimumab achieved 2-year RFS (51.5% vs. 43.8%) and 3-year RFS (46.5% vs. 34.8%).

Researchers observed the DFS benefit associated with ipilimumab among patients in each disease subgroup. Patients with microscopic disease in lymph nodes demonstrated a 33% reduction in the risk for recurrence, whereas patients with macroscopic involvement demonstrated a 17% reduced risk for recurrence.

More patients assigned ipilimumab experienced grade 3 or grade 4 treatment-related gastrointestinal (15.9% vs. 0.8%), hepatic (10.6% vs. 0.2%) and endocrine (8.5% vs. 0%) adverse events. Although most adverse events were manageable, only 56% of endocrine events — which included hypophysitis and hypothyroidism — were resolved.

“Endocrine events may linger for a long time because patients may require hormone replacement therapies for years,” Eggermont said. “This is an important consideration.”

More than half of the patients (52%) assigned ipilimumab discontinued treatment due to adverse events, 38.6% of whom discontinued within the first 12 weeks. Five patients (1.1%) died due to a treatment-related toxicity.

Distant metastases-free survival and OS will be reported later with longer follow-up, Eggermont said. Another trial is ongoing to evaluate two different doses of ipilimumab.