Median PFS was 13.8 versus 7.2 months in the combination arm compared to the sunitinib arm (HR = 0.61; p < .0001) in the patients with programmed cell death-ligand 1 positive (PD-L1+) tumours, while median PFS in patients irrespective of PD-L1 expression was 13.8 versus 8.4 months (HR = 0.69; p = .0001) respectively. Confirmed objective response rate 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 RCC,” remarked Dr. Robert Motzer, presenter and study lead from Memorial Sloan Kettering Cancer Center, New York City, US. “The findings support the potential of avelumab plus axitinib as a new treatment approach for patients with advanced RCC. The combination benefit was shown in all subgroups of patients, by independent review as well as by investigators, and whether tumour cells stained positive for PD-L1 or not,” he continued.Despite available therapies, the outlook for patients with advanced RCC 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 TKI, and TKIs have been the mainstay of treatment. “TKIs, and checkpoint blockers like avelumab, both may have potential immune-modulating functions that, when combined, may provide clinical benefit in patients with advanced RCC that exceeds the effects of the respective drugs alone, without compromising toxicity,” said Motzer.
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 schedule of four weeks on followed by two weeks off (4/2). The primary outcomes were PFS 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.
Prof. Thomas Powles, consultant oncologist at Barts Health NHS Trust, London, UK, commented on the results. “The results are eye catching. The response rates are twice as good as previous standards of care, and progression-free survival is entering into very impressive territory for a randomised trial. This approach involves giving combinations of most active agents upfront, therefore there is uncertainty around whether this will translate into a similarly impressive survival signal, as seen with other immunotherapy combinations.”
1. Abstract LBA6_PR ‘JAVELIN Renal 101: A randomized, phase III study of avelumab + axitinib vs sunitinib as first-line treatment of advanced renal cell carcinoma (aRCC)’ will be presented by Robert Motzer during Presidential Symposium on Sunday 21 October, 16:30 to 18:10 (CEST) in Room 18 - Hall A2. Annals of Oncology, Volume 29 Supplement 8 October 2018
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