Five months after its EMA approval, GNE’s KADCYLA for metastatic breast cancer is experiencing mixed fortunes in Europe.
This week, the HAS released its KADCYLA appraisal, granting the product and ASMR II due to its strong OS benefit vs. TYKERB and XELODA (+5.8 months, HR 0.682, p=0.0006) in mBC patients having previously received HERCEPTIN and a taxane. No oncology agent has received an ASMR II from the HAS since MABTHERA for follicular lymphoma in 2012.
Meanwhile, in England, KADCYLA failed to overcome NICE’s cost-effectiveness hurdle. In the appraisal, NICE specifically called out KADCYLA as “not working well enough to justify its high cost” of GBP 90,000 per course. The issue here is that, unlike the HAS, NICE was specifically looking for effectiveness in the subgroup of 2ndline patients in KADCYLA’s EMILIA trial, rather than the overall trial population which also included patients receiving KADCYLA as a 3rd line or later therapy. NICE noted that the analysis in this 2nd line subpopulation may not have been sufficiently powered to detect a difference in treatment effect, and in fact may suggest a lesser benefit than in the overall study population.
Interestingly, KADCYLA’s assessment by IQWiG – notorious for stringent evidence requirements in well-defined patient subpopulations – did not run into this particular barrier. IQWiG instead chose to divide KADCYLA’s patient subpopulations by stage of disease and nature of prior therapy, rather than by line of therapy, granting the product a score of ‘considerable benefit’ in one subpopulation.
These latest decisions continue to exemplify the different approaches that manufacturers must take when attempting to satisfy the value demonstration requirements of different European HTA bodies.