1890P - Switch-maintenance therapy with nivolumab in TKI-sensitive patients with metastatic renal cell carcinoma (mRCC): Subgroup analysis for PD-L1 status of a randomized phase II study (NIVOSWITCH)

Background

In mRCC patients combinations of tyrosine kinase inhibitors (TKI) and checkpoint inhibitors (CPI) are standards of care. We previously reported on our switch-maintenance approach (CPI after TKI) in mRCC. Today, we report on exploratory analyses that investigated predictive value of the PD-L1 status.

Methods

Pts. with measurable clear cell mRCC, ECOG 0-2, adequate organ function and partial remission or stable disease to TKI therapy were eligible. 49 patients were randomized to early study termination between 12/2016 and 08/2018. After 12 weeks, 1:1 randomization to TKI continuation (24 pts.) or nivolumab (NIVO; 25 pts.; 240 or 480 mg IV q2-4wk) was performed. PD-L1 expression was determined by immunohistochemistry using the SP163 antibody clone and defined as combined positivity score (CPS) with setting 1 as cut-point for positivity (n=41). Objective response rate (ORR) was assessed according to RECIST 1.1. KM and log-Rank analyses were used for survival analyses.

Results

Median age was 65 years (range 35 - 79), 82% were male and 4% had ECOG PS 2. With metastases predominantly in lung (47%), lymph nodes (27%) and liver (24%). 55% received sunitinib. ORR for NIVO vs. TKI differed when assessed from randomization (16 vs. 48%; P=0.03). Accordingly, progression free survival (PFS) from randomization was 3.0 vs. 11.9 mo. (HR = 2.57 [95% CI: 1.36 – 4.89]) in favor for TKI continuation. With a 2-year OS of 64% for NIVO vs. 66% for TKI (HR = 1.12 [95% CI: 0.43 – 2.89]; P=0.82). ORR in CPS<1 vs >1 RCC was 13.3% and 40.0% for NIVO and 37.5% and 75.0% in TKI cases. Tumors with a CPS<1 most frequently showed PD as the best response in both arms. However, a greater proportion of patients reported PD for NIVO (n=9, 60.0%) compared to TKI (n=1, 12.5%).

Conclusions

Continuation of TKI is more efficacious than early switch to NIVO, despite PD-L1 positivity. The major limitation of our trial is the premature closure and its limited sample size. Authoring Group Name: IAG-N of the German Cancer Society Sponsor, funding source: AIO-Studien-gGmbH, financial support BMS

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors, IAG-N of the German Cancer Society.

Funding

AIO-Studien-gGmbH, financial support BMS.

Disclosure

C. Darr: Financial Interests, Personal, Other: Ipsen, Janssen. All other authors have declared no conflicts of interest.