Clinical activity of nivolumab in patients with non-clear cell renal cell carcinoma

Abstract

BackgroundNivolumab is approved for patients with metastatic renal cell carcinoma (mRCC) refractory to prior antiangiogenic therapy. The clinical activity of nivolumab in patients with non-clear cell RCC subtypes remains unknown as these patients were excluded from the original nivolumab trials.MethodsPatients from 6 centers in the United States who received at least one dose of nivolumab for non-clear cell mRCC between 12/2015 and 06/2017 were identified. A retrospective analysis including patient characteristics, objective response rate according to RECIST v1.1 and treatment-related adverse events (TRAEs) was undertaken.ResultsForty-one patients were identified. Median age was 58 years (33–82), 71% were male, and majority had ECOG PS 0 (40%) or 1 (47%). Histology included 16 papillary, 14 unclassified, 5 chromophobe, 4 collecting duct, 1 Xp11 translocation and 1 MTSCC (mucinous tubular and spindle cell carcinoma). Among 35 patients who were evaluable for best response, 7 (20%) had PR and 10 (29%) had SD. Responses were observed in unclassified, papillary and collecting duct subtypes. In the entire cohort, median follow-up was 8.5 months and median treatment duration was 3.0 months. Median PFS was 3.5 months and median OS was not reached. Among responders, median time to best response was 5.1 months, and median duration of response was not reached as only 2 out of 7 responders had disease progression during follow-up. TRAEs of any grade were noted in 37% and most commonly included fatigue (12%), fever (10%) and rash (10%). Nivolumab treatments were postponed in 34% and discontinued in 15% of patients due to intolerance. No treatment-related deaths were observed.ConclusionsNivolumab monotherapy demonstrated objective responses and was well tolerated in a heterogeneous population of patients with non-clear cell mRCC. In the absence of other data in this treatment setting, this study lends support to the use of nivolumab for patients with metastatic non-clear cell renal cell carcinoma.

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.…”

Safety and efficacy of nivolumab for metastatic renal cell carcinoma: real‐world results from an expanded access programme

“…The 26 cases with mRCC with non‐clear‐cell histology in our series showed a slightly inferior response rate of 19.2% vs 23.1% of the overall population, suggesting that nivolumab is an active agent for these tumours, even if longer follow‐up is needed to obtain mature data on OS. Other authors have recently reported an objective response in seven (20%) of 35 patients with non‐clear‐cell mRCC treated with nivolumab, but even in that study follow‐up was too short to have data on OS . Larger series including different histological subtypes with longer follow‐up are needed to better characterize the biological activity of nivolumab in these subsets of tumours.…”

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.…”