medwireNews: Findings from the JAVELIN Renal 101 trial of patients with advanced renal cell carcinoma (RCC) suggest front-line use of avelumab plus axitinib is superior to sunitinib for patients with sarcomatoid histology and for those who did not undergo upfront cytoreductive nephrectomy.
The subgroup analyses were presented as posters at the ESMO Congress 2019 in Barcelona, Spain, and follow the earlier results showing a progression-free survival (PFS) and objective response rate (ORR) benefit that led to approval for the combination in both the USA and Europe.
Presenting author Toni Choueiri, from the Dana-Farber Cancer Institute in Boston, Massachusetts, USA, and co-workers explained that sarcomatoid RCC histology is an “aggressive phenotype” that does not respond well to VEGF or VEGFR inhibitors.However, analysis of the 12.2% of JAVELIN Renal 101 participants with sarcomatoid components or features showed that the 47 patients randomly assigned to receive avelumab plus axitinib had significantly better median PFS than the 61 patients given sunitinib (7.0 vs 4.0 months, hazard ratio [HR]=0.57).
Compared with sunitinib, the combination regimen was associated with both a greater ORR (46.8 vs 21.3%), and a faster response (median 1.6 vs 3.1 months) which lasted 2.4 months longer on average than the response achieved with sunitinib. The 12-month overall survival (OS) rate was also higher with avelumab plus axitinib versus sunitinib, at 83.0% versus 67.0%.
Laurence Albiges discusses a JAVELIN Renal 101 subgroup analysis (2:30).
This independent video interview was supported by an educational grant from Pfizer and Merck KGaA.
“These findings are comparable to those of other analyses of first-line ICI [immune checkpoint inhibitor] therapy in this patient population, with consistently improved efficacy [versus] a standard-of-care VEGF pathway inhibitor,” the researchers said.
Choueiri et al therefore suggested “that the combination of avelumab [plus] axitinib may counteract the aggressive features of [sarcomatoid] RCC that hinder efficacy of standard-of-care RCC treatments.”
Results were also reported at the meeting for a second JAVELIN Renal 101 subgroup of patients who had not undergone upfront cytoreductive nephrectomy. Laurence Albiges, from Institut Gustave Roussy in Villejuif, France, and colleagues explained that this post hoc analysis included 20.2% of the trial participants, of whom 90 were given avelumab plus axitinib and 89 sunitinib.
After a minimum 6 months of follow-up, the ORR was higher with the combination regimen, with partial responses achieved in 32.7% of patients versus 11.3% of those given sunitinib.
A 30% or greater renal target lesion shrinkage occurred in 34.5% versus 9.7% of these groups after a median of 4.4 and 7.1 months, respectively. And the duration of this 30% or greater shrinkage was 3.7 months longer on average with avelumab plus axitinib, the team says.
The researchers wrote that none of the patients in the combination arm had 20% or greater tumor enlargement during follow-up compared with 3.2% of those given sunitinib.
Moreover, PFS was higher with avelumab plus axitinib with regard to both the renal target lesions (12.8 vs 10.9 months, HR=0.43) and for all lesions (11.1 vs 6.9 months, HR not significant). Median OS at time of analysis was unreached in both treatment arms; 18-month OS was achieved by 64.1% of the patients given the combination regimen and 53.8% of sunitinib-treated patients.
Albiges et al summarized that the primary tumor shrinkage and duration of response raises “potential interest in ICI/[tyrosine kinase inhibitor] combination therapy for patients with in situ primary renal tumors” and “provide insight into future neoadjuvant strategies in [advanced] RCC.”
An open-label, single arm phase II trial is now planned to assess avelumab plus axitinib as a neoadjuvant therapy for localized RCC patients, they added.
Both poster presentations continued the biomarker analysis previously reported for the JAVELIN Renal 101 study, showing again that increased CD8 expression on tumor infiltrating cells was associated with improved PFS in both the sarcomatoid and no upfront surgery groups.
However, unlike the primary analysis of the full study cohort, the JAVELIN Renal 101 genetic signature was not predictive of PFS for the subgroup of patients who did not undergo upfront cytoreductive nephrectomy.
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This independent news article was supported by an educational grant from Pfizer and Merck KGaA
ESMO Congress 2019; Barcelona, Spain: 27 September–1 October