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A phase II trial of intermittent nivolumab in patients with metastatic renal cell carcinoma (mRCC) who have received prior anti-angiogenic therapy.

ABSTRACT: BACKGROUND:Nivolumab is approved for mRCC patients who have received prior anti-angiogenic therapy but the duration of therapy required for sustained clinical benefit is unknown. A phase II clinical trial to investigate the feasibility of intermittent nivolumab dosing was conducted. METHODS:Patients ?18?years of age with mRCC who were previously treated with at least one antiangiogenic therapy were eligible. Patients were treated with nivolumab for twelve weeks. Patients who had RECIST PD were removed from the trial. Patients who did not initially achieve ?10% reduction in tumor burden (TB) continued nivolumab per standard of care. Patients with ?10% TB reduction entered a treatment-free observation phase with re-imaging every 12?weeks. Nivolumab was restarted in patients with a???10% TB increase and again held with TB reduction ?10%. This intermittent nivolumab dosing continued until RECIST PD while on nivolumab. The primary objective was feasibility of intermittent nivolumab, defined as the proportion of patients eligible for intermittent therapy who elect to receive intermittent nivolumab. Intermittent nivolumab would be considered "feasible" if the acceptance rate was ?80%. Forty patients provides >?95% power with 0.05 type I error, assuming a null acceptance rate of 50%. With the approval of the combination of ipilimumab/nivolumab (April 2018) in front-line mRCC, this cohort was closed prior to completed pre-planned approval. RESULTS:Of the 14 patients enrolled, 13 (93%) were male with a median age 65. All had a prior nephrectomy and 12 (86%) were intermediate-risk by IMDC criteria. Five patients (36%) met the criteria for the intermittent phase of the trial (median TB decrease 46%) and all agreed to intermittent therapy. With a median follow-up of 48?weeks, only one patient restarted therapy. The four remaining patients have a sustained response for a median of 34?weeks (range, 16-53) off therapy. No patients developed RECIST PD while off therapy. CONCLUSIONS:This prospective experience of intermittent nivolumab dosing in mRCC supports further investigation of intermittent immunotherapy dosing strategies in RCC. TRIAL REGISTRATION:NCT03126331 (Intermittent Nivolumab in Metastatic Renal Cell Carcinoma Patients; Date of registration 4/27/2017; https://clinicaltrials.gov/ct2/show/NCT03126331 ).

SUBMITTER: Ornstein MC

PROVIDER: S-EPMC6524207 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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A phase II trial of intermittent nivolumab in patients with metastatic renal cell carcinoma (mRCC) who have received prior anti-angiogenic therapy.

Ornstein Moshe C MC Wood Laura S LS Hobbs Brian P BP Allman Kimberly D KD Martin Allison A Bevan Michael M Gilligan Timothy D TD Garcia Jorge A JA Rini Brian I BI

Journal for immunotherapy of cancer 20190516 1

<h4>Background</h4>Nivolumab is approved for mRCC patients who have received prior anti-angiogenic therapy but the duration of therapy required for sustained clinical benefit is unknown. A phase II clinical trial to investigate the feasibility of intermittent nivolumab dosing was conducted.<h4>Methods</h4>Patients ≥18 years of age with mRCC who were previously treated with at least one antiangiogenic therapy were eligible. Patients were treated with nivolumab for twelve weeks. Patients who had R ...[more]

PMID: 31097024

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Project description:BackgroundSalvage nivolumab and ipilimumab after prior anti-PD-1/PD-L1 therapy is frequently used off-label for clear cell metastatic renal cell carcinoma (mRCC). However, limited data are available to guide such therapy. We performed a meta-analysis to characterize further the safety and efficacy of salvage nivolumab and ipilimumab.MethodsWe conducted a systematic review in accordance with PRISMA. Studies of salvage nivolumab and ipilimumab in patients with mRCC published in English before June 1, 2021 were included. We also included patients treated at the Ohio State University from 2012 to 2020 through a retrospective chart review. The included studies were further stratified into adaptive and standard groups based on their designs. We calculated objective response rate (ORR) and adverse events (AEs) via pooled data and quantitative synthesis using the Stata metaprop procedure. A conservative random effect model was used to combine values.ResultsA total of 7 studies and 310 patients were included. Salvage nivolumab and ipilimumab had an ORR of 14% (95% CI, 0.09-0.21) and median progression-free survival ranged between 3.7 and 5.5 months. Four out of the seven studies were standard design, whereas the other three studies were adaptive. The ORR was numerically higher in the standard group compared with the adaptive group (21% and 9-10%, respectively). The responses to salvage nivolumab and ipilimumab did not correlate with the initial anti-PD-1/PD-L1 responses (odds ratio = 1.45; p = 0.5). Grade ≥3 AEs occurred in 26% of the patients (95% CI, 0.19-0.33). There were no new safety signals observed in this study.ConclusionSalvage nivolumab and ipilimumab demonstrated moderate antitumor activity and a manageable safety profile in patients with mRCC who had prior anti-PD-1/PD-L1 therapy.Implication for practicePatients with metastatic renal cell carcinoma have limited treatment options after progressive disease on anti-PD-1/PD-L1 therapy. The role of salvage nivolumab and ipilimumab in this patient population is poorly defined. The studies on this highly important and clinically relevant topic are limited by small sample sizes. The results from our meta-analysis suggest that nivolumab and ipilimumab are feasible in the salvage setting with moderate efficacy and acceptable toxicity profile. The response rates differ with different treatment designs. This information will be beneficial to guide clinical decision-making and accurately estimating toxicity.

Dataset Information

A phase II trial of intermittent nivolumab in patients with metastatic renal cell carcinoma (mRCC) who have received prior anti-angiogenic therapy.

Publications

A phase II trial of intermittent nivolumab in patients with metastatic renal cell carcinoma (mRCC) who have received prior anti-angiogenic therapy.

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