medwireNews: Results of the JAVELIN Renal 101 trial indicate that patients with a new diagnosis of advanced renal cell carcinoma (RCC) have better outcomes when treated with the combination of avelumab and axitinib than with sunitinib.
Robert Motzer (Memorial Sloan Kettering Cancer Center, New York, USA), who presented the findings at the ESMO 2018 Congress in Munich, Germany, highlighted that the improvements were seen regardless of programmed cell death ligand 1 (PD-L1) status and that the combination had “a favorable safety profile.”
He therefore believes that avelumab plus axitinib could be “a new first-line standard of care for patients with advanced RCC.”
Discussing the results, Viktor Grünwald (University Hospital Essen, Germany) said that the evidence for the efficacy of avelumab–axitinib was “convincing” and that the tolerability was “one of the beauties of this combination.”
As such, it “should be available for our patients,” he commented, but noted that without data on overall survival or health-related quality of life benefit, “it is uncertain whether the [combination] is ready for prime time.”
In the phase III trial, patients with treatment-naïve advanced RCC with a clear-cell component were randomly assigned to receive either 6-week cycles of avelumab 10 mg/kg every 2 weeks plus axitinib 5 mg twice a day or sunitinib 50 mg daily on a 4 weeks on, 2 weeks off regimen; the corresponding median follow-up durations were 9.9 and 8.4 months.
Treatment with the anti-PD-L1 agent avelumab plus the VEGFR inhibitor axitinib led to a significant 39% reduction in the risk for disease progression or death as assessed by independent review relative to sunitinib among the 560 participants who had at least 1% of PD-L1-positive immune cells, with median progression-free survival (PFS) times of 13.8 versus 7.2 months.
Combination therapy also boosted the objective response rate (ORR) in the PD-L1-positive population, at 55% versus 26% for sunitinib.
These improvements were also observed in the overall trial population comprising 886 patients, with a median PFS of 13.8 and 8.4 months in the avelumab–axitinib and sunitinib groups, respectively, giving a hazard ratio for progression or death of 0.69, and corresponding ORRs of 51% and 26%.
The overall survival data had not attained maturity at the time of analysis, and although the discussant noted “a clear trend” in favor of the combination arm, he stressed that the data could not be judged properly as yet.
In terms of the safety profile, grade 3–4 adverse events (AEs) were reported in 55% of combination-treated patients and by an identical proportion of those given sunitinib; three patients in the combination group had a grade 5 AE, as did one person in the sunitinib group.
Additionally, the rate of discontinuation of all study drugs due to toxicity was low, at 4% and 8% in the avelumab–axitinib and sunitinib arms, respectively, as was the proportion of patients who stopped just avelumab or axitinib, at 13.8% and 6.9%.
Nine percent of participants in the avelumab–axitinib group experienced immune-related AEs of grade 3 or 4, and 11% needed high-dose corticosteroids for the management of immune-related AEs, Motzer reported.
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