Lister J1, Pafitas S2, Meng J3, Wiecek W4, Schmidt E5, Zagorska A6, Marteau F7
1Certara, Lörrach, BW, Germany, 2Analytica Laser, a Certara company, Lörrach, BW, Germany, 3LASER Analytica, Loerrach, Germany, 4Analytica Laser, London, UK, 5Analytica LASER, Loerrach, Germany, 6Ipsen, Paris, France, 7Ipsen Pharma SAS, Boulogne-Billancourt, France
OBJECTIVES : Cabozantinib has been approved in the EU as a first-line treatment option for intermediate- or poor-risk advanced renal cell carcinoma (aRCC). This approval is based on its significant superiority in progression-free survival (PFS) to sunitinib in the CABOSUN trial. Cabozantinib has also demonstrated superior PFS to all other tyrosine kinase inhibitors in a network meta-analysis (NMA). Here, we report findings from a systematic literature review (SLR) and NMA covering trials of ten therapies for first-line aRCC, including the immunotherapy combinations ipilimumab + nivolumab (recently approved) and atezolizumab + bevacizumab (in development). METHODS : For comparison with the combination therapies, two NMA methods were employed for each risk profile: 1) a fixed-effect model on hazard ratios (HRs); and 2) a fixed-effect comparison of survival curves. The outcomes analysed were overall survival (OS), PFS and objective response rate (ORR). RESULTS : Of 22 studies identified by the SLR, 16 were selected for inclusion in the NMA. Using method 1, cabozantinib provided significantly longer PFS in terms of HRs in the overall population and intermediate-/poor-risk subgroups than all current aRCC therapies. The HR for OS was increased versus all comparators except ipilimumab + nivolumab, although none of the differences were statistically significant. For ORR, the odds ratios favoured cabozantinib over sunitinib, ipilimumab + nivolumab and atezolizumab + bevacizumab; again, these findings were not statistically significant. Using method 2, OS was increased for cabozantinib except versus nivolumab + ipilimumab, whereas PFS was improved for cabozantinib versus all other comparators. CONCLUSIONS : The updated NMA confirms a significant benefit of cabozantinib in PFS of patients with aRCC versus all first-line treatments, including immunotherapy, with no statistically significant differences in OS. Head-to-head clinical trials are needed to provide robust clinical data for comparing cabozantinib with other first-line therapies.
Conference/Value in Health Info
2019-11, ISPOR Europe 2019, Copenhagen, Denmark
Oncology, Urinary/Kidney Disorders