Saturday, April 22, 2017
Ipi - 3mg vs 10mg/kg - Increased OS with increased SE on 10!
Initially, folks with melanoma were treated with 10mg/kg of ipilimumab (now called Yervoy). Side effects were clearly pretty bad for some on that regimen, so the powers that were...with the evidence that was...decided the difference in result was not worth suffering the side effects that resulted with 10mg/kg and going with the 3mg/kg dose for Stage IV peeps was the better part of valor. For reasoning that makes sense only when dealing with the FDA....Stage III folks were still allowed (or forced...however you want to look at it) to take the 10mg/kg dose, because that was all that had been used in existing testing for them at that time.
Ipilimumab 10 mg/kg versus ipilimumab 3 mg/kg in patients with unresectable or metastatic melanoma: a randomised, double-blind, multicentre, phase 3 trial. Ascierto, Del Vecchio, Robert, et al. Lancet Oncol. 2017 Mar 27.
A phase 2 trial suggested increased overall survival and increased incidence of treatment-related grade 3-4 adverse events with ipilimumab 10 mg/kg compared with ipilimumab 3 mg/kg in patients with advanced melanoma. We report a phase 3 trial comparing the benefit-risk profile of ipilimumab 10 mg/kg versus 3 mg/kg.
This randomised, double-blind, multicentre, phase 3 trial was done in 87 centres in 21 countries worldwide. Patients with untreated or previously treated unresectable stage III or IV melanoma, without previous treatment with BRAF inhibitors or immune checkpoint inhibitors, were randomly assigned (1:1) with an interactive voice response system by the permuted block method using block size 4 to ipilimumab 10 mg/kg or 3 mg/kg, administered by intravenous infusion for 90 min every 3 weeks for four doses. Patients were stratified by metastasis stage, previous treatment for metastatic melanoma, and Eastern Cooperative Oncology Group performance status. The patients, investigators, and site staff were masked to treatment assignment. The primary endpoint was overall survival in the intention-to-treat population and safety was assessed in all patients who received at least one dose of study treatment. This study is completed and was registered with ClinicalTrials.gov, number NCT01515189.
Between Feb 29, and July 9, 2012, 727 patients were enrolled and randomly assigned to ipilimumab 10 mg/kg (365 patients; 364 treated) or ipilimumab 3 mg/kg (362 patients; all treated). Median follow-up was 14·5 months for the ipilimumab 10 mg/kg group and 11·2 months for the ipilimumab 3 mg/kg group. Median overall survival was 15·7 months for ipilimumab 10 mg/kg compared with 11·5 months for ipilimumab 3 mg/kg. The most common grade 3-4 treatment-related adverse events were diarrhoea (37 [10%] of 364 patients in the 10 mg/kg group vs 21 [6%] of 362 patients in the 3 mg/kg group), colitis (19 [5%] vs nine [2%]), increased alanine aminotransferase (12 [3%] vs two [1%]), and hypophysitis (ten [3%] vs seven [2%]). Treatment-related serious adverse events were reported in 133 (37%) patients in the 10 mg/kg group and 66 (18%) patients in the 3 mg/kg group; four (1%) versus two (<1 adverse="" died="" events.="" from="" i="" patients="" treatment-related="">1>
In patients with advanced melanoma, ipilimumab 10 mg/kg resulted in significantly longer overall survival than did ipilimumab 3 mg/kg, but with increased treatment-related adverse events. Although the treatment landscape for advanced melanoma has changed since this study was initiated, the clinical use of ipilimumab in refractory patients with unmet medical needs could warrant further assessment.
So....from these results...it looks as though the overall survival difference was about 4 months or less ~ 15·7 months for ipilimumab 10 mg/kg compared with 11·5 months for ipi 3mg/kg. To be honest, not sure what I would choose if I had to (or COULD) choose.
Wishing you my best....whatever you do, dear ratties! (Will we EVER get to stop being ratties????!) - c