JAVELIN Renal 101
In untreated advanced RCC, does avelumab + axitinib improve PFS versus sunitinib?
Biomarker / PD-L1
PD-L1 expression was a prespecified biomarker and part of the primary analysis population. PD-L1-positive disease was defined as PD-L1 expression on ≥1% of immune cells. The primary endpoints were PFS and OS in the PD-L1-positive population, with key secondary analyses in the overall population. Of 886 patients, 270 and 290 patients in the two arms had PD-L1-positive tumours in the updated analysis. The combination's PFS benefit was also demonstrated in the overall population.
Absolute Effect
Long-term PFS: The 5-year event-free rates remained separated. OS numerically favored the combination but did not reach statistical significance.
OS: Final analysis did not demonstrate a statistically significant OS difference; subsequent therapies likely contributed to attenuation of OS separation.
Safety: Grade ≥3 treatment-related AEs were 66.8% vs 61.5%. Patient-reported outcomes were similar between groups.
Interpretation & limitations
The trial demonstrates durable disease-control and response differences without a statistically significant OS advantage. The 5-year PFS event-free rate is the appropriate fixed-time basis for the displayed NNT.
Primary source
Motzer RJ, et al. N Engl J Med. 2019;380:1103–1115; final analysis.