medwireNews: The combination of avelumab and axitinib results in significantly better progression-free survival (PFS) than that seen with sunitinib in treatment-naïve patients with advanced renal cell carcinoma (RCC) irrespective of programmed cell death ligand 1 (PD-L1) status, shows the JAVELIN Renal 101 trial.
The 886 participants of the phase III study – of whom 560 tested positive for PD-L1 (≥1% of immune cells) – were randomly assigned to receive either avelumab 10 mg/kg every 2 weeks alongside axitinib 5 mg twice daily in 6-week cycles or sunitinib 50 mg/day on a 4 weeks on, 2 weeks off schedule, and followed up for a respective 9.9 and 8.4 months.
The co-primary endpoint of independent review-assessed PFS in the PD-L1-positive subgroup was a median of 13.8 months for patients given the anti-PD-L1 agent avelumab plus the vascular endothelial growth factor receptor tyrosine kinase inhibitor axitinib.
This was significantly longer than the median PFS of 7.2 months for those treated with sunitinib, and equated to a hazard ratio (HR) of 0.61 in favour of the combination.
The PFS benefit with avelumab plus axitinib remained significant in the overall trial population, at a median of 13.8 months versus 8.4 months with sunitinib, and an HR of 0.69.
And treatment with the combination almost doubled the objective response rate relative to sunitinib in both the PD-L1-positive group and the overall trial population, at 55% versus 26% and 51% versus 26%, respectively.
The data for overall survival – the other primary endpoint – were not mature at the time of analysis.
Presenting the results at the ESMO 2018 Congress in Munich, Germany, Robert Motzer, from Memorial Sloan Kettering Cancer Center in New York, USA, noted that avelumab plus axitinib also had “a favorable safety profile.”
The incidence of grade 3 or 4 treatment-related adverse events (AEs) was the same in the combination and sunitinib arms, at 55%, and grade 5 events occurred in three patients given the combination and one patient given sunitinib.
The corresponding rates of discontinuation of all study drugs due to AEs were 4% and 8%.
Motzer reported that immune-related AEs of grade 3 or 4 were observed in 9% of the combination group, and that the incidence of colitis and hepatotoxicity was low. Furthermore, just 11% of patients required high-dose corticosteroids for immune-related AEs, he added.
In light of the efficacy and safety profile of avelumab plus axitinib, the presenter concluded that their findings support the combination as “a new first-line standard of care for patients with advanced RCC.”
Discussant Viktor Grünwald, from University Hospital Essen in Germany, noted the “convincing efficacy” of the combination, which is seen in the absence of a “substantial increase in toxicity”, but questioned whether combining the agents really is better than administering them sequentially.
To answer this question, we need to have either an overall survival improvement or quality of life benefit, and in the absence of these data “it is uncertain whether the [combination] is ready for prime time”, he concluded.
Motzer RJ, Penkov K, Haanen J, et al. JAVELIN Renal 101: a randomized, phase 3 study of avelumab + axitinib vs sunitinib as first-line treatment of advanced renal cell carcinoma (aRCC). ESMO 2018 Congress, 19-23 October, Munich, Germany (LBA6_PR).
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