Evaluation of brain metastasis in JAVELIN Renal 101: Efficacy of avelumab + axitinib (A+Ax) versus sunitinib (S).

Abstract

687 Background: Patients (pts) with brain metastasis from renal cell carcinoma (RCC) have poor prognosis and are often excluded from randomized registrational trials. The phase 3 JAVELIN Renal 101 trial (NCT02684006) demonstrated significantly improved progression-free survival (PFS) for A+Ax vs S in pts with advanced RCC (Motzer NEJM 2019). The activity of A+Ax in pts with brain metastasis enrolled in JAVELIN Renal 101 is presented. Methods: PFS was compared between treatment arms for the subgroup of pts randomized in JAVELIN Renal 101 with brain metastases at enrollment (pts with brain disease site prior to randomization by blinded independent central review [BICR] or by investigator assessment). PFS time was summarized per BICR assessment by treatment arm using the Kaplan-Meier method. The Cox proportional hazards model was fitted to compute the hazard ratio (HR) and the corresponding CI. In addition, time to brain metastasis was assessed for pts without brain metastasis by BICR at enrollment after treating death as a competing risk. Results: Of all randomized pts (A+Ax arm, N=442; S, N=444), 23 in each arm (5.2%) had asymptomatic brain metastasis at enrollment; of these, pts assigned to A+Ax had a PFS of 4.9 mo (95% CI: 1.6, 5.7) vs 2.8 mo (95% CI: 2.3, 5.6) for pts assigned to S (HR: 0.90; 95% CI: 0.43, 1.88). Among pts without brain metastasis at enrollment, 8 pts on the A+Ax arm and 10 on the S arm developed brain metastasis during the trial, based on BICR assessment; 17/18 occurred ≤12 mo from randomization. The cumulative incidence rate of brain metastasis at 18 mo was 2% (95% CI: 0.6, 3.3) for the A+Ax arm and 3% (95% CI: 1.1, 4.8) for the S arm. Conclusions: In this post hoc exploratory analysis of JAVELIN Renal 101, the observed PFS among pts with brain metastasis at enrollment was similar between the two arms, with HR and median PFS numerically favoring A+Ax. Pts on the S arm had a numerically higher incidence of new brain metastases on trial. Outcomes are poor in pts with advanced RCC and brain metastasis; more effective treatments are needed. Clinical trial information: NCT02684006.