A real world example of coverage with evidence development in Australia - ipilimumab for the treatment of metastatic melanoma.

Background: Australian Government subsidisation of ipilimumab for the treatment of patients with metastatic melanoma was conditional on the sponsor entering a 'managed entry scheme' to assess the 2-year overall survival rate in metastatic melanoma patients who received ipilimumab in the first year of Pharmaceutical Benefits Scheme listing.

Methods: All unresectable stage IIIc / IV metastatic melanoma patients treated with at least one dose of ipilimumab therapy in Australia from the PBS listing date to a time point 12 months later (i.e. from 1-Aug-2013 to 31-Jul-2014) were invited to participate. Overall survival at 2 years post treatment initiation was measured, with Cox regression analysis used to examine the relationship between survival and patient baseline characteristics.

Results: The evaluable population (910 patients) was on average 63.3 years old, male (70.1%) and treated in a public hospital (64.4%) in an urban area (76.5%). The majority of patients were treatment naïve (63.3%), did not have brain metastases (71.1%), and were classified as ECOG performance status 0 or 1 (90.4%). The 2 year overall survival rate was conservatively calculated to be at least 23.9% and potentially as high as 34.2%. A significant difference in overall survival at 2 years was demonstrated across the categories of ECOG performance status ( p  < 0.0001), M-status ( p  = 0.0005) and treatment status ( p  = 0.0114). No statistical difference in survival rate was observed when examining brain metastases vs no brain metastases ( p  = 0.2622), treatment at private vs public hospitals ( p  = 0.7601) nor treatment in the urban vs rural setting ( p  = 0.5048).

Conclusions: The 2 year overall survival rate for all patients receiving PBS subsidised ipilimumab in Australia from the first year Pharmaceutical Benefits Scheme cohort is estimated to be between 23.9% and 34.2%, which is higher than the 23.5% observed in the key ipilimumab registrational trial. Results and learnings from the ipilimumab 'managed entry scheme' illustrate that early access with the promise of future evidence to confirm a medicine's cost-effectiveness can work, but needs to be carefully considered, constructed and managed.