JAVELIN Renal 101 Results

In both the PD-L1-positive population (560 individuals) and the overall population (886 individuals), patient baseline characteristics were well balanced with respect to prior nephrectomy, Eastern Cooperative Oncology Group (ECOG) performance status, and prognostic risk based on 2 risk classifications — from the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) and from MSKCC. Approximately two-thirds of patients were in the intermediate prognostic risk group and approximately 20% were in the favorable risk group.1

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Median follow-up was 9.9 months for patients in the combination avelumab and axitinib arm and 8.4 months for patients treated with sunitinib.

For the coprimary PFS end point, median PFS was 13.8 months with the drug combination compared with 7.2 months for sunitinib alone. With a hazard ratio (HR) of 0.61, the combination of avelumab and axitinib reduced the risk of progression or death by 39% (P < .0001).1 The PFS end point reported for the overall population also mirrored that seen in the PD-L1+ population (IRC determined median PFS: 13.8 months for the combination vs 8.4 months for sunitinib (HR, 0.69; P = .0001).

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The investigator-reported PFS for the PD-L1+ population and for the overall population was also consistent with the IRC-assessed PFS. Median PFS for the PD-L1 group was 13.3 months for the combination and 8.2 months for sunitinib alone (HR, 0.51; P < .0001), while median PFS for the overall group was 12.5 months for the combination and 8.4 months for sunitinib alone (HR, 0.64; P < .0001).

The PFS was similar regardless of PD-L1 status and the study suggested that the combination of avelumab and axitinib was appropriate for all treatment-naive patients with advanced RCC.  In key subgroups (PD-L1 status, IMDC risk, MSKCC risk), the HR also favored the combination of avelumab and axitinib.

The coprimary end point of OS in patients with PD-L1–positive advanced RCC was immature at the time of the interim report.

ORR was doubled for patients receiving avelumab and axitinib. For the PD-L1 group the ORR was 55% for patients receiving avelumab and axitinib versus 26% for patients receiving axitinib. For the overall population, corresponding ORR was 51% and 26%.

In the PD-L1 cohort, complete response (CR) was reported in 4% of patients receiving the combination and 2% of patients receiving sunitinib. “The complete response of 4% is anticipated to increase as the follow-up of responders becomes longer,” Dr Motzer said.

Median time to response was 1.6 months, and 108 patients (73%) who saw an ongoing response remain on the study.

Grade 3 treatment-related adverse events were reported in 51% of patients receiving the combination and 48% of patients receiving sunitinib. Corresponding grade 4 event rates were 4% and 7%. Treatment discontinuation was lower for patients on the combination: 4% for the combination vs 8% for sunitinib.

Immune-related adverse events were seen in 38% of patients receiving the combination, with hypothyroidism and liver function test abnormalities occurring in 21% and 5% of patients, respectively. High-dose corticosteroids to manage immune-mediated toxicities were administered to 11% of patients.

No new adverse events were reported outside those seen with single agents in other studies, and the combination was well tolerated, Dr Motzer noted.  

“PFS was longer and ORR was higher for avelumab plus axitinib in the PD-L1 and overall population. The results were in concordance between the IRC and investigators. The benefit was seen regardless of PD-L1 status and across all prognostic risk groups,” Dr Motzer summarized.