Chicago, IL—The results of a phase 3 clinical trial support the use of avelumab (Bavencio) plus axitinib (Inlyta) as a new first-line standard-of-care treatment for patients with newly diagnosed advanced renal-cell carcinoma. According to data presented at ASCO 2019, JAVELIN Renal 101 demonstrated longer progression-free survival (PFS) and higher overall response rates for the combination of avelumab with axitinib versus sunitinib (Sutent) monotherapy for treatment-naïve patients with advanced renal-cell carcinoma. The benefit was not limited only to the first-line setting. Patients who received avelumab plus axitinib also had longer PFS after second-line treatment and a longer mean duration of response than patients who received sunitinib alone.
“PFS and response rate benefit was observed in all patients, regardless of PD-L1 status and regardless of prognostic risk group,” said Toni K. Choueiri, MD, Director, Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Boston, MA. “Overall, we feel that these data provide novel insight into the biological response to avelumab and axitinib,” he added.
Previous data from this trial had demonstrated improved outcomes with the combination of avelumab and axitinib versus sunitinib monotherapy. For this new analysis, researchers sought to determine which patients may benefit most from the combination therapy, by looking at certain biomarkers, including PD-L1 expression, CD8 expression, gene-expression profiling, and other mutations and polymorphisms. All biomarkers were drawn from tumor tissue samples collected within 1 year of screening and before receiving treatment.
PFS Increased Regardless of PD-L1 or Risk Status
When stratified by risk status, the median PFS for patients in the highest-risk group was 6 months with avelumab and axitinib versus 2.9 months with sunitinib. In the intermediate-risk group, the median PFS also favored the combination therapy versus sunitinib—13.8 months versus 8.4 months, respectively. Finally, among favorable-risk patients, the median PFS had not yet been reached in the combination arm versus 13.8 months in the sunitinib arm.
Additional subgroup analyses all favored the combination arm. No differences in survival were seen among patients with PD-L1–positive or PD-L1–negative disease with the combination; patients with renal-cell carcinoma and PD-L1 expression who received sunitinib had significantly shorter PFS than patients with no PD-L1 expression (P = .0037). Patients with more CD8-expressing cells also had significantly longer PFS than patients with fewer CD8-expressing cells in the combination arm, but no difference was observed in the sunitinib arm.
In addition, a smaller proportion of patients in the combination arm received subsequent anticancer therapies compared with the sunitinib-alone arm. The most frequently used subsequent anticancer therapies were cabozantinib (Cabometyx) in the combination arm and nivolumab (Opdivo) in the sunitinib arm.
PFS-2: New Measure for Second-Line Treatment
Dr Choueiri and colleagues also investigated whether the benefit of treatment in the first-line setting had any impact on PFS after treatment with second-line agents, based on a novel measure called “PFS-2.”
“In theory, a first-line treatment could change the biology of the disease and therefore lead to substantially shorter benefit of second-line treatment,” said Dr Choueiri, noting that this measure is a potentially important end point for regulatory and reimbursement evaluation.
According to the new analysis, patients who received avelumab plus axitinib also had longer PFS-2 and mean duration of response than those who received sunitinib. The mean duration of response with avelumab and axitinib combination treatment was more than 4 months longer than sunitinib, with a minimum of 6 months’ follow-up.
“Given the durable responses observed and the flat curves of the combination treatment, it’s reasonable to believe that there will be more improvement in mean duration of response versus sunitinib with a longer follow-up time,” Dr Choueiri added. “Furthermore, PD-L1–positive patients who received avelumab with axitinib had more frequent and deeper responses than those who received sunitinib.”
The most frequently reported treatment-related adverse events of any grade with the combination were diarrhea, hypertension, and fatigue. Hypothyroidism was the most common immune-related adverse event.
Dr Choueiri noted that only 4% of patients in the combination arm discontinued both drugs because of a treatment-related adverse event compared with 8% of patients who discontinued sunitinib.