ESMO 2018: JAVELIN Renal 101: Avelumab Plus Axitinib in Previously Untreated Renal Cell Carcinoma


Key Points

  • Median PFS was 13.8 vs 7.2 months in the combination arm compared to the sunitinib arm in the patients with PD-L1–positive tumors.
  • Median PFS in patients irrespective of PD-L1 expression was 13.8 vs 8.4 months, respectively.
  • Confirmed objective response rate was 55.2% and 25.5%, respectively.

A combination of the immune checkpoint blocker avelumab (Bavencio) plus the tyrosine kinase inhibitor axitinib (Inlyta) improved progression-free survival (PFS) in previously untreated patients with advanced renal cell carcinoma (RCC) in the phase III JAVELIN Renal 101 study, according to results presented by Motzer et al at the European Society for Medical Oncology (ESMO) 2018 Congress (Abstract LBA6_PR).

“JAVELIN Renal 101 is the first positive phase III study combining an immune checkpoint blocker with a tyrosine kinase inhibitor compared to tyrosine kinase inhibitor [treatment] alone in the first-line treatment of advanced RCC,” remarked lead author Robert Motzer, MD, of Memorial Sloan Kettering Cancer Center, in a statement. “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 tumor cells stained positive for programmed cell death ligand 1 (PD-L1) or not,” he continued.

“Tyrosine kinase inhibitors [like axitinib] 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 Dr. Motzer.

JAVELIN Renal 101 Methods

In the global, randomized JAVELIN Renal 101 trial, 886 patients with kidney cancer with all MSKCC (Memorial Sloan Kettering Cancer Center/Motzer score used for selection of patients with metastatic RCC 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 every 2 weeks in combination with axitinib 5 mg orally twice daily. The comparator group of 444 patients received sunitinib (Sutent) given at 50 mg orally once a day on a schedule of 4 weeks on followed by 2 weeks off. The primary outcomes were PFS in patients testing positive for PD-L1 expression patients (up to 30 months); and overall survival in PD-L1–positive patients up to 5 years.


Median PFS was 13.8 vs 7.2 months in the combination arm compared to the sunitinib arm (hazard ratio [HR] = 0.61; P < .0001) in the patients with PD-L1–positive tumors, while median PFS in patients irrespective of PD-L1 expression was 13.8 vs 8.4 months (HR = 0.69; P = .0001) respectively. Confirmed objective response rate was 55.2% (95% confidence interval [CI] = 49.9–61.2) and 25.5% (95% CI = 20.6–30.9), respectively.

Treatment-emergent adverse events of grade 3 and over were experienced by 71.2% vs 71.5% of patients in the combination arm vs the sunitinib arm, respectively, and led to discontinuation of drug in 22.8% vs 13.4%, respectively.


Thomas Powles, MBBS, MRCP, MD, consultant oncologist at Barts Health NHS Trust, London, commented on the results in a statement. “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 randomized 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.”

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