In a phase 1b trial, Avelumab ( Bavencio ) plus Axitinib ( Inlyta ) as first-line had encouraging antitumor activity for patients with advanced renal cell carcinoma ( aRCC ) ( Lancet Oncol 2018;19:451 ).
Eligible patients with clear-cell aRCC, ECOG less than or equal to 1, and no prior systemic therapy were randomized 1:1 ( stratified by ECOG and geographic region ) to receive Avelumab 10 mg/kg IV Q2W plus Axitinib 5 mg PO BID ( oraly twice daily ) in 6-week cycles or Sunitinib ( Sutent ) 50 mg PO QD ( once a day ) on schedule 4/2; all prognostic risk groups were included.
Primary endpoints were progression-free survival ( PFS; by blinded independent central review [ BICR ] per RECIST v1.1 ) and overall survival ( OS ) in patients with PD-L1+ tumors ( greater than or equal to 1% of immune cells ).
Secondary endpoints included progression-free survival by BICR and overall survival irrespective of PD-L1 expression, objective response ( OR ), and safety.
As of 20 Jun 2018, 886 patients were randomized ( Avelumab plus Axitinib: N = 442; Sunitinib: N = 444); of these, 21/62/16% had favorable / intermediate / poor IMDC risk criteria ( not reported in less than 1% ).
In 560 patients ( 63.2% ) with PD-L1+ tumors, median progression-free survival was 13.8 vs 7.2 months in Avelumab plus Axitinib versus Sunitinib arms, respectively ( hazard ratio, HR = 0.61; p less than 0.0001 ).
Median progression-free survival in patients irrespective of PD-L1 expression was 13.8 vs 8.4 months ( HR = 0.69; p = 0.0001 ).
Progression-free survival and objective response results favored Avelumab plus Axitinib in patients irrespective of PD-L1 expression and in all MSKCC / IMDC prognostic risk groups.
Overall survival data were immature at data cutoff ( less than 16% of patients with events ).
In Avelumab plus Axitinib versus Sunitinib arms, grade greater than or equal to 3 treatment-emergent adverse events occurred in 71.2% vs 71.5% of patients and led to discontinuation of any study drug in 22.8% vs 13.4%; deaths due to study treatment toxicity occurred in 0.7% vs 0.2% of patients.
In conclusion, this randomized phase 3 trial met its primary objective of significantly improving progression-free survival in patients with PD-L1+ aRCC treated with Avelumab plus Axitinib versus Sunitinib.
Progression-free survival and objective response benefit was also observed in patients irrespective of PD-L1 expression and across all prognostic risk groups.
The safety profiles were consistent with those of prior studies of each drug.
These results support Avelumab plus Axitinib as a potential new first-line standard-of-care for patients with advanced renal cell carcinoma. ( Xagena )
Source: European Society of Medical Oncology - ESMO Congress, 2018