ASCO GU 2020: Evaluation of Brain Metastasis in JAVELIN Renal 101: Efficacy of Avelumab + Axitinib versus Sunitinib

San Francisco, CA (UroToday.com) Patients with brain metastasis from renal cell carcinoma have a poor prognosis and are usually excluded from randomized trials. A large multi-institutional retrospective analysis of almost 1600 patients with metastatic renal cell carcinoma across 68 clinical trials identified 72 patients (4.5%) with brain metastasis at the screening. Their median overall survival was 10.3 months and their one-year overall survival was 48%.

Nivolumab has shown minimal activity in 39 patients with untreated brain metastasis with an intracranial objective response rate of 11.8% and an extracranial objective response rate of 21.2%.

The phase 3 JAVELIN renal 101 trial (NCT02684006) (figure 1) demonstrated significantly improved progression-free survival with avelumab (an anti-PD1) +axitinib vs. sunitinib in patients with advanced renal cell carcinoma (HR 0.69, 95% CI 0.56-0.84, p<0.001).

JAVELIN renal 101 trial design

Figure 1. JAVELIN renal 101 trial

In the presented trial patients with previously diagnosed brain metastasis were eligible for enrolment if they had completed their treatment and had recovered from the acute effects of radiation therapy or surgery prior to randomization. Patients who were newly diagnosed with brain metastasis or those with known symptomatic brain metastasis requiring steroids were not eligible for enrolment.

Of all randomized patients (avelumab + axitinib, n=442, and sunitinib arm, n=444), 23 In each arm had asymptomatic brain metastasis at enrollment. The baseline demographics of the patients in the study are shown in table 1.

Table 1. Baseline demographics of patients with brain metastases at enrollment

baseline demographics of patients with brain metastasis

Among all patients without brain metastases at enrollment, 8 patients in the avelumab arm and 10 patients in the sunitinib arm developed brain metastases during the trial period. The cumulative incidents rate of brain metastasis at 18 months was 1.95% in the avelumab arm and 2.93% in the Sunitinib arm (figure 6). The progression-free survival and overall survival are shown in Figures 2 and 3, respectively.

PFS per BICR in patients with brain metastasis

Figure 2. Progression-free survival per BICR in patients with brain metastasis at enrollment

OS in patients with brain metastasis

Figure 3. Overall survival in patients with brain metastasis at enrollment

CIR of developing brain metastasis

Figure 6. Cumulative incidence rate (CIR) of developing brain metastasis per BICR

The authors concluded that the observed progression-free survival among patients with brain metastasis at enrollment was similar between the two arms, with a hazard ratio and medium progression-free survival numerically favoring the avelumab arm. Patients in the sunitinib arm had a numerically higher incidence of new brain metastasis. The outcomes have been shown to be poor in patients with advanced renal cell carcinoma and brain metastasis, therefore, more effective treatments are needed

Presented by: Eric Jonasch, MD, Professor, Department of Genitourinary Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas

Written By: Hanan Goldberg, MD, Urology Department, SUNY Upstate Medical University, Syracuse, NY, USA, Twitter: @GoldbergHanan at the 2020 Genitourinary Cancers Symposium, ASCO GU #GU20, February 13-15, 2020, San Francisco, California

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