A combination of the immune checkpoint blocker, Avelumab ( Bavencio ), plus the tyrosine kinase inhibitor ( TKI ), Axitinib ( Inlyta ), significantly improves progression-free survival ( PFS ) in previously untreated patients with advanced renal cell carcinoma ( RCC ) in a phase 3 study.
Median progression-free survival was 13.8 versus 7.2 months in the combination arm compared to the Sunitinib ( Sutent ) arm ( hazard ratio, HR = 0.61; p less than 0.0001 ) in the patients with programmed cell death-ligand 1 positive ( PD-L1+ ) tumours, while median progression-free survival in patients irrespective of PD-L1 expression was 13.8 versus 8.4 months ( HR = 0.69; p = 0.0001 ) respectively.
Confirmed objective response rate ( ORR ) was 55.2 ( CI 95%: 49.9, 61.2 ) and 25.5 ( CI 95%: 20.6, 30.9 ) respectively.
JAVELIN Renal 101 is the first positive phase 3 study combining an immune checkpoint blocker with a TKI compared to TKI alone in the first line treatment of advanced renal cell cancer.
Despite available therapies, the outlook for patients with advanced renal cell cancer remains poor with less than 10% of patients surviving at five years post-diagnosis.
New treatment options are needed.
Avelumab is an IgG1 monoclonal antibody against the programmed cell death protein ligand PD-L1 ( checkpoint blocker ), while Axitinib is a tyrosine kinase inhibitor ( TKI ), and TKIs have been the mainstay of treatment.
In the JAVELIN Renal 101 global, randomised trial, 886 kidney cancer patients with all MSKCC ( Memorial Sloan Kettering Cancer Center / Motzer score used for selection of mRCC patients for trial inclusion ) prognostic subgroups ( good, intermediate, and poor risk ) were enrolled and were administered therapy as first-line treatment.
Avelumab was administered to 442 patients at 10 mg/kg intravenously ( IV ) every two weeks in combination with Axitinib, 5 mg orally twice daily.
The comparator group of 444 patients received Sunitinib given at 50 mg orally once a day on a schedule of four weeks on followed by two weeks off ( 4/2 ).
The primary outcomes were progression-free survival in PD-L1+ patients ( up to 30 months ); and overall survival in PD-L1+ patients up to five years.
Treatment-emergent adverse events of grade 3 and over were experienced by 71.2% versus 71.5% of patients in the combination versus Sunitinib arms respectively, and led to discontinuation of drug in 22.8% versus 13.4% respectively. ( Xagena )
Source: European Society of Medical Oncology - ESMO Congress, 2018