The Clinical Activity of PD-1/PD-L1 Inhibitors in Metastatic Non–Clear Cell Renal Cell Carcinoma

Abstract

Programmed death 1 (PD-1) and PD ligand 1 (PD-L1) inhibitors have shown activity in metastatic clear cell renal cell carcinoma (ccRCC). Data on the activity of these agents in patients with non-clear cell RCC (nccRCC) or patients with sarcomatoid/rhabdoid differentiation are limited. In this multicenter analysis, we explored the efficacy of PD-1/PD-L1 inhibitors in patients with nccRCC or sarcomatoid/rhabdoid differentiation. Baseline and follow-up demographic, clinical, treatment, and radiographic data were collected. The primary endpoint was objective response rate. Secondary endpoints include time-to-treatment failure (TTF), overall survival (OS), and biomarker correlates. Forty-three patients were included: papillary ( = 14; 33%), chromophobe ( = 10; 23%), unclassified ( = 9; 21%), translocation ( = 3; 7%), and ccRCC with sarcomatoid differentiation ( = 7, 16%). Of those 43 patients, 11 patients (26%) had sarcomatoid and/or rhabdoid differentiation ( = 7 with ccRCC; = 4 nccRCC). Overall, 8 patients (19%) objectively responded, including 4 patients (13%) who received PD-1/PD-L1 monotherapy. Responses were observed in patients with ccRCC with sarcomatoid and/or rhabdoid differentiation ( = 3/7, 43%), translocation RCC ( = 1/3, 33%), and papillary RCC ( = 4/14, 29%). The median TTF was 4.0 months [95% confidence interval (CI), 2.8-5.5] and median OS was 12.9 months (95% CI, 7.4-not reached). No specific genomic alteration was associated with clinical benefit. Modest antitumor activity for PD-1/PD-L1-blocking agents was observed in some patients with nccRCC. Further prospective studies are warranted to investigate the efficacy of PD-1/PD-L1 blockade in this heterogeneous patient population. .

Nivolumab for the Treatment of Patients with Metastatic Non-Clear Cell Renal Cell Carcinoma (nccRCC): A Single-Institutional Experience and Literature Meta-Analysis

“…Even though only six patients were treatment naive, they had a numerically higher ORR ( n = 3/6, 50%) in comparison with the reported ORR with sunitinib in nccRCC. We also report that the ORR and DCR were 18.6% and 53.4%, respectively, in a meta‐analysis of 124 patients from published series of metastatic nccRCC and ccRCC >20% rhabdoid patients treated with PD‐1/PD‐L1 checkpoint inhibitors . The observed best ORR with nivolumab in patients with metastatic nccRCC is consistent with the reported activity in ccRCC .…”

“…In our review of the literature, we identified two retrospective studies in patients with metastatic nccRCC who received PD‐1/PD‐L1 checkpoints blockade that reported the best ORR by tumor histology . We identified 124 patients with nccRCC and ccRCC histology with >20% rhabdoid and 112 patients with evaluable response rates to PD‐1/PD‐L1 checkpoint inhibitors to be included in our meta‐analysis.…”

“…Hence, patients with metastatic nccRCC have limited therapeutic options and have not been included in the trials that established the clinical activity of nivolumab in metastatic RCC. Currently, the evidence for the clinical efficacy and safety of immune checkpoint inhibitors in nccRCC is based on two retrospective studies that included patients with nccRCC and also those with ccRCC with sarcomatoid features that were treated with any PD‐1/PD‐L1 checkpoint inhibitors, showing acceptable safety and interesting clinical efficacy in specific nccRCC histologies . Therefore, we aimed to assess the clinical efficacy of nivolumab in patients with metastatic nccRCC who were treated at MD Anderson Cancer Center.…”

Construction of immune‐related risk signature for renal papillary cell carcinoma

“…Immunotherapies such as programmed death‐1 (PD‐1)/programmed death ligand 1 (PD‐L1) inhibitors or tumor vaccine are becoming favorable novel treating approach for KIRP. The PD‐1/PD‐L1 blockade demonstrated modest antitumor activity in KIRP patients, with the response rate being approximately 30%, which are much higher than that of clear cell type. Besides, other studies found that a tumor vaccine called TroVax® which expressed the 5 T4 tumor‐associated antigen exhibited robust efficacy and safety in renal cell cancer patients including KIRP patients in clinical trials .…”

Potential Roles for PD-1 Inhibition and Cabozantinib in Patients with Metastatic Non-Clear Cell Renal Cell Carcinoma

“…In this issue of The Oncologist , Dr. Chahoud and colleagues report their experience using nivolumab alone or in combination with ipilimumab or VEGF‐targeted therapies to treat patients with metastatic nccRCC at MD Anderson Cancer Center (MDACC) . Because their study is the third retrospective analysis of nivolumab in metastatic nccRCC, the authors also performed a meta‐analysis of these studies . In the MDACC experience, the objective response rate (ORR) was 20.6%, with a complete response (CR) rate of 8% in a heavily pretreated cohort in which 50% of patients received nivolumab as third‐line or later treatment.…”