Avelumab plus Axitinib versus Sunitinib for Advanced Renal-Cell Carcinoma

Abstract

BACKGROUND In a single-group, phase 1b trial, avelumab plus axitinib resulted in objective responses in patients with advanced renal-cell carcinoma. This phase 3 trial involving previously untreated patients with advanced renal-cell carcinoma compared avelumab plus axitinib with the standard-of-care sunitinib. METHODS We randomly assigned patients in a 1:1 ratio to receive avelumab (10 mg per kilogram of body weight) intravenously every 2 weeks plus axitinib (5 mg) orally twice daily or sunitinib (50 mg) orally once daily for 4 weeks (6-week cycle). The two independent primary end points were progression-free survival and overall survival among patients with programmed death ligand 1 (PD-L1)–positive tumors. A key secondary end point was progression-free survival in the overall population; other end points included objective response and safety. RESULTS A total of 886 patients were assigned to receive avelumab plus axitinib (442 patients) or sunitinib (444 patients). Among the 560 patients with PD-L1–positive tumors (63.2%), the median progression-free survival was 13.8 months with avelumab plus axitinib, as compared with 7.2 months with sunitinib (hazard ratio for disease progression or death, 0.61; 95% confidence interval [CI], 0.47 to 0.79; P<0.001); in the overall population, the median progression-free survival was 13.8 months, as compared with 8.4 months (hazard ratio, 0.69; 95% CI, 0.56 to 0.84; P<0.001). Among the patients with PD-L1–positive tumors, the objective response rate was 55.2% with avelumab plus axitinib and 25.5% with sunitinib; at a median follow-up for overall survival of 11.6 months and 10.7 months in the two groups, 37 patients and 44 patients had died, respectively. Adverse events during treatment occurred in 99.5% of patients in the avelumab-plus-axitinib group and in 99.3% of patients in the sunitinib group; these events were grade 3 or higher in 71.2% and 71.5% of the patients in the respective groups. CONCLUSIONS Progression-free survival was significantly longer with avelumab plus axitinib than with sunitinib among patients who received these agents as first-line treatment for advanced renal-cell carcinoma. (Funded by Pfizer and Merck [Darmstadt, Germany]; JAVELIN Renal 101 ClinicalTrials.gov number, .)

C‐reactive protein/albumin ratio is a predictive factor for prognosis in patients with metastatic renal cell carcinoma

“…The main purpose of the four‐tier model was the separation of prognosis in patients in the IMDC intermediate‐risk group in the immunotherapy era. Within a year, we need to select “avelumab/pembrolizumab + axitinib” or “nivolumab + ipilimumab” for the patients in the intermediate/poor risk groups . Currently, the recommendation of optimal treatment selection in those patients is not available.…”

Avelumab plus axitinib vs sunitinib for advanced renal cell carcinoma: Japanese subgroup analysis from JAVELIN Renal 101

“…The study design and patient eligibility criteria have been described in detail previously . This was a multicenter, randomized, open‐label, phase 3 trial comparing avelumab + axitinib with sunitinib.…”

“…Preliminary data from a single‐arm phase 1b study of avelumab + axitinib in treatment‐naive patients with advanced RCC showed a manageable safety profile and encouraging antitumor activity, with an objective response rate (ORR) of 58% . The randomized phase 3 JAVELIN Renal 101 clinical trial of avelumab + axitinib vs sunitinib in previously untreated patients with advanced RCC demonstrated longer PFS (median, 13.8 vs 7.2 months; stratified hazard ratio [HR], 0.61; P < 0.001) and higher ORR (55.2% vs 25.5%) with the combination vs sunitinib in patients with PD‐L1+ tumors . PFS and ORR benefits were also observed in patients irrespective of PD‐L1 expression.…”

Novel Risk Scoring System for Patients with Metastatic Renal Cell Carcinoma Treated with Immune Checkpoint Inhibitors

“…Immunotherapy has changed the landscape of treatment of metastatic renal cell carcinoma (mRCC) since nivolumab, a programmed cell death protein‐1 (PD‐1) inhibitor, was approved for vascular endothelial growth factor (VEGF)–refractory mRCC in November 2015 . The first immune checkpoint inhibitor (ICI) combination regimen, nivolumab and ipilimumab, was recently approved for first‐line intermediate or poor risk mRCC, and results from ongoing trials of ICI and anti‐VEGF combination regimens have been very promising . Given the increasing number of treatment options for patients with mRCC, including several ICI‐based regimens, it is becoming increasingly important to identify risk factors that make patients with mRCC more likely to respond to ICI.…”