Updated efficacy results from the JAVELIN Renal 101 trial: first-line avelumab plus axitinib versus sunitinib in patients with advanced renal cell carcinoma

Abstract

Background: The phase 3 JAVELIN Renal 101 trial ( NCT02684006 ) demonstrated significantly improved progression-free survival (PFS) with first-line avelumab plus axitinib versus sunitinib in advanced renal cell carcinoma (aRCC). We report updated efficacy data from the second interim analysis. Patients and methods: Treatment-naive patients with aRCC were randomized (1 : 1) to receive avelumab (10 mg/kg) 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 PFS and overall survival (OS) among patients with programmed death ligand 1–positive (PD-L1+) tumors. Key secondary end points were OS and PFS in the overall population. Results: Of 886 patients, 442 were randomized to the avelumab plus axitinib arm and 444 to the sunitinib arm; 270 and 290 had PD-L1+ tumors, respectively. After a minimum follow-up of 13 months (data cut-off 28 January 2019), PFS was significantly longer in the avelumab plus axitinib arm than in the sunitinib arm {PD-L1+ population: hazard ratio (HR) 0.62 [95% confidence interval (CI) 0.490–0.777]}; one-sided P < 0.0001; median 13.8 (95% CI 10.1–20.7) versus 7.0 months (95% CI 5.7–9.6); overall population: HR 0.69 (95% CI 0.574–0.825); one-sided P < 0.0001; median 13.3 (95% CI 11.1–15.3) versus 8.0 months (95% CI 6.7–9.8)]. OS data were immature [PD-L1+ population: HR 0.828 (95% CI 0.596–1.151); one-sided P = 0.1301; overall population: HR 0.796 (95% CI 0.616–1.027); one-sided P = 0.0392]. Conclusion: Among patients with previously untreated aRCC, treatment with avelumab plus axitinib continued to result in a statistically significant improvement in PFS versus sunitinib; OS data were still immature. Clinical Trial number: NCT02684006 .

Systemic treatment of advanced/metastatic renal cell carcinoma in the context of SARS-CoV-2 pandemic: recommendations from the interdisciplinary working group for renal tumors (IAG-N)

“…In light of CheckMate214, JAVELINRenal 101 and Keynote-426 studies, no significant overall survival (OS) benefit was gained by any of the immune combinations for patients with a favorable risk profile (HR for OS: ipilimumab/nivolumab vs. sunitinib: 1.19 (95% CI 0.77-1.85), axitinib/pembrolizumab vs. sunitinib: 0.94 (95% CI 0.43-2.07), axitinib/avelumab vs. sunitinib: 0.812 (95% CI 0.336-1.960) (Motzer et al 2020;Keytruda-EMEA 2020;Choueiri et al 2020). A major limitation of these data are the short follow-up duration, which limits the data interpretation.…”

“…In cases who exert favorable clinical parameters depicted Choueiri et al 2018Choueiri et al , 2020. To minimize the risk of immune-mediated adverse events, as well as high dose steroids application due to immune related adverse events, a careful patients based valuing is demanded to choose the best treatment regimen (Table 2).…”

Baseline plasma levels of soluble PD-1, PD-L1, and BTN3A1 predict response to nivolumab treatment in patients with metastatic renal cell carcinoma: a step toward a biomarker for therapeutic decisions

“…17,18 Ongoing clinical trials and others recently concluded continue to study the efficacy of novel drug combinations, with special reference to the anti-PD-L1 agent avelumab or the anti-PD-1 antibody pembrolizumab with the VEGFR-inhibitor axitinib. 19,20 However, although a clinically relevant median response duration is reported, not all patients equally benefit from the currently available IO treatment, and the patient response rate is overall low. 17 Biological factors specific for certain individuals have a clear effect on this variation in response.…”

<p>Immunotherapeutic Targets and Therapy for Renal Cell Carcinoma</p>

“…[10][11][12][13][14][15][16] Immune checkpoint inhibitors, which already represent a standard treatment option in pretreated mRCC patients, are also revolutionizing the frontline treatment, since combination immunotherapy as well as combinations of immunotherapy with targeted agents have been shown to significantly improve the outcomes of treatment-naïve mRCC patients. [11][12][13][14][15][16] In RCC, immunotherapy influences adaptive immunity, allowing the immune system to recognize tumor antigens, maintain memory, and kill neoplastic cells. 17 Activation of adaptive immunity against foreign antigens is consequent to a complex chain of events, involving several receptors present on both neoplastic cells and immune cells, mediating inhibitory or activator signals.…”