Improved Survival with Ipilimumab in Patients with Metastatic Melanoma
- Study type
- Clinical trial
- Study name
- MDX010-20
- Phase
- Phase 3
- Design
- Randomised phase 3 trial with 3:1:1 randomisation (ipilimumab plus gp100, ipilimumab alone, gp100 alone)
- Sample size
- 676 patients
- Source
- N Engl J Med · 2010
- Trial registration
- NCT00094653
In plain words
In this study, the drug ipilimumab, which strengthens the body's immune system to fight cancer cells, was tested in people with advanced melanoma for whom earlier treatments had not worked. People who received ipilimumab lived on average about 10 months, while in the comparison group (gp100 vaccine alone) this was 6.4 months. This drug can cause serious immune side effects that sometimes last a long time, but most of them can be reversed with proper treatment, so it needs close monitoring by a doctor.
Key results
Treatment arms and regimens
Ipilimumab 3 mg/kg IV (90-minute infusion) every 3 weeks for up to 4 doses (induction) + gp100 vaccine: two modified HLA-A*0201-restricted peptides, 1 mg each, emulsified in incomplete Freund's adjuvant (Montanide ISA-51), given subcutaneously (gp100:209-217(210M) in the right thigh and gp100:280-288(288V) in the left thigh) immediately after the infusion (403 patients). Patients with stable disease for 3 months after week 12 or a confirmed partial/complete response could receive re-induction with the same regimen on later progression.
Ipilimumab 3 mg/kg IV (90-minute infusion) every 3 weeks for up to 4 doses (induction), without gp100 vaccine (137 patients); re-induction possible under the same criteria.
gp100 vaccine: two modified HLA-A*0201-restricted peptides, 1 mg each, emulsified in incomplete Freund's adjuvant (Montanide ISA-51), given subcutaneously (gp100:209-217(210M) in the right thigh and gp100:280-288(288V) in the left thigh) immediately after a placebo infusion, on the same schedule every 3 weeks for up to 4 doses (136 patients).
Source of the regimen details: Full text of the paper (PMC3549297) and ClinicalTrials.gov NCT00094653
Doses are given for the information of specialists, as in this study’s protocol, and are not a prescription. Every drug must be prescribed by the treating physician for the individual patient.
Study population
Adults with unresectable stage III or IV HLA-A*0201-positive melanoma who had been treated with one prior regimen containing dacarbazine, temozolomide, fotemustine, carboplatin or interleukin-2 and had progressed during treatment for metastatic disease; ECOG 0 or 1, life expectancy of at least 4 months, normal haematological, hepatic and renal function and no systemic therapy in the past 28 days; ocular melanoma, prior anti-CTLA-4 therapy or cancer vaccine, and autoimmune disease were excluded.
Endpoints
Primary endpoint: overall survival. Other endpoints are not reported in the abstract.
Safety and side effects
Grade 3 or 4 immune-related adverse events occurred in 10 to 15% of patients treated with ipilimumab and in 3% of patients in the gp100-alone group. 14 deaths related to the study drugs (2.1%) were reported, 7 of which were associated with immune-related adverse events.
Clinical significance and place in guidelines
This trial showed that ipilimumab improves overall survival in previously treated metastatic melanoma, a result that had not been achieved before. Adding the gp100 vaccine showed no benefit over ipilimumab alone. Careful management of immune-related adverse events is essential. The current status of approvals and guideline recommendations should be checked separately, as the abstract does not mention them.
Limitations
The comparator was gp100 alone rather than a standard treatment with a proven effect on survival. The study population was limited to HLA-A*0201-positive patients. Other limitations are not reported in the abstract and should be checked in the full text.
This summary was prepared by the editorial team from the published paper; the original paper is the final reference. Read the original abstract on PubMed.