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Efficacy and safety data in elderly patients with metastatic renal cell carcinoma included in the nivolumab Expanded Access Program (EAP) in Italy.

ABSTRACT: BACKGROUND:Results from phase III clinical trial CheckMate 025 have established nivolumab as the standard of care for treatment of metastatic renal-cell carcinoma (mRCC) after VEGF inhibitor failure; however, elderly patients are under-represented in the registration trial and little is known about the activity of nivolumab in this subgroup. The purpose of the Expanded Access Program was to provide nivolumab to patients with mRCC who had progressed despite treatment with other agents that were considered standard of care. METHODS:Nivolumab 3 mg/kg was administered intravenously every 2 weeks to a maximum of 24 months or until progression or unacceptable toxicity. The current analysis included all patients from the EAP Italian cohort who had received ?1 dose of nivolumab. Adverse events (AEs) were monitored using Common Terminology Criteria for Adverse Events v4.0. RESULTS:A total of 389 patients with advanced RCC were enrolled in the Italian cohort of the EAP and treated with nivolumab. Of these patients, 125 (32%) were at least 70 years of age and 70 (18%) were at least 75 years of age. Efficacy with nivolumab in the elderly patients was similar to that observed in the overall EAP population and in the CheckMate 025 trial. Safety was comparable between the elderly patients and the overall EAP population, and was consistent with what previously reported. CONCLUSION:The final results suggest that elderly patients with pretreated metastatic RCC may benefit from therapy with nivolumab.

SUBMITTER: Vitale MG

PROVIDER: S-EPMC6034807 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Efficacy and safety data in elderly patients with metastatic renal cell carcinoma included in the nivolumab Expanded Access Program (EAP) in Italy.

Vitale Maria Giuseppa MG Scagliarini Sarah S Galli Luca L Pignata Sandro S Lo Re Giovanni G Berruti Alfredo A Defferrari Carlotta C Spada Massimiliano M Masini Cristina C Santini Daniele D Ciuffreda Libero L Ruggeri Enzo Maria EM Bengala Carmelo C Livi Lorenzo L Fagnani Daniele D Bonetti Andrea A Giustini Lucio L Hamzaj Alketa A Procopio Giuseppe G Caserta Claudia C Sabbatini Roberto R

PloS one 20180706 7

<h4>Background</h4>Results from phase III clinical trial CheckMate 025 have established nivolumab as the standard of care for treatment of metastatic renal-cell carcinoma (mRCC) after VEGF inhibitor failure; however, elderly patients are under-represented in the registration trial and little is known about the activity of nivolumab in this subgroup. The purpose of the Expanded Access Program was to provide nivolumab to patients with mRCC who had progressed despite treatment with other agents tha ...[more]

PMID: 29979712

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Project description:BackgroundThe Italian Renal Cell Cancer Early Access Program was an expanded access program that allowed access to nivolumab, for patients (pts) with metastatic renal cell carcinoma (mRCC) prior to regulatory approval.MethodsPts with previously treated advanced or mRCC were eligible to receive nivolumab 3 mg/kg every 2 weeks. Pts included in the analysis had received ≥1 dose of nivolumab and were monitored for drug-related adverse events (drAEs) using CTCAE v.4.0. Immune-related (ir) AEs were defined as AEs displaying a certain, likely or possible correlation with immunotherapy (cutaneous, endocrine, hepatic, gastro-intestinal and pulmonary). The association between overall survival (OS) and irAEs was assessed, and associations between variables were evaluated with a logistic regression model.ResultsA total of 389 pts were enrolled between July 2015 and April 2016. Overall, the objective response rate was 23.1%. At a median follow-up of 12 months, the median progression-free survival was 4.5 months (95% CI 3.7-6.2) and the 12-month overall survival rate was 63%. Any grade and grade 3-4 drAEs were reported in 124 (32%) and 27 (7%) of pts, respectively, and there were no treatment-related deaths. Any grade irAEs occurred in 76 (20%) of patients, 8% cutaneous, 4% endocrine, 2% hepatic, 5% gastro-intestinal and 1% pulmonary. Of the 22 drAEs inducing treatment discontinuation, 10 (45%) were irAEs. Pts with drAEs had a significantly longer survival than those without drAEs (median OS 22.5 versus 16.4 months, p = 0.01). Pts with irAEs versus without irAEs had a more significant survival benefit (median OS not reached versus 16.8 months, p = 0.002), confirmed at the landmark analysis at 6 weeks. The occurrence of irAEs displayed a strong association with OS in univariable (HR 0.48, p = 0.003) and multivariable (HR 0.57, p = 0.02) analysis.ConclusionsThe appearance of irAEs strongly correlates with survival benefit in a real-life population of mRCC pts treated with nivolumab.

Project description:BackgroundThe incidence of Merkel cell carcinoma (MCC), a rare form of skin cancer with a poor prognosis, has increased in Italy in recent decades. Avelumab, an anti-programmed death ligand 1 monoclonal antibody, is approved for the treatment of metastatic MCC (mMCC) based on the results of the phase 2 JAVELIN Merkel 200 trial. The global avelumab expanded access program (EAP) was designed to provide compassionate use of avelumab prior to approval for patients with mMCC who had limited treatment options. We report findings from a subgroup of Italian patients enrolled in the avelumab EAP.MethodsEligible patients had mMCC and progressive disease following ≥ 1 prior line of chemotherapy or were ineligible for chemotherapy or clinical trial participation. Patients received avelumab 10 mg/kg intravenously every 2 weeks. Treating physicians were provided with an initial 3-month supply of avelumab; resupply was permitted if the patient achieved a complete response, partial response, stable disease, or other clinical benefit per physician assessment. Safety and efficacy data for the EAP were reported at the treating physician's discretion.ResultsBetween April 1, 2016, and September 14, 2018, 109 requests for avelumab were received from Italy, and 102 were approved. All but 1 of the approved patients had received ≥ 1 prior line of therapy. At data cutoff (March 22, 2019), 95 patients had been supplied with avelumab and response data were available for 55 patients. The objective response rate in response-evaluable patients was 29.1%, including 6 patients (10.9%) who achieved a complete response and 10 patients (18.2%) who achieved a partial response; in the total population supplied with avelumab (n = 95), the proportion who had an objective response was 16.8%. The median duration of treatment in responding patients was 9.7 months (range, 3.5-41.7 months). The most frequently reported treatment-related adverse events were infusion-related reaction (single preferred term; n = 3 [3.2%]) and pyrexia (n = 2 [2.1%]).ConclusionsResults from Italian patients enrolled in the avelumab EAP are consistent with the findings of the JAVELIN Merkel 200 trial and confirm the efficacy and safety of avelumab treatment in this population.

Project description:Atezolizumab is a treatment for locally advanced/metastatic urothelial carcinoma (mUC). However, its use in patients with renal insufficiency or UC with mixed variant histology (MVH) is not well characterized. To report efficacy and safety of atezolizumab in these special subpopulations from an expanded access program (EAP). A total of 218 patients were enrolled at 36 US study sites (November 2015-August 2016), and the trial ended following the approval of atezolizumab by the US Food and Drug Administration. This post hoc analysis investigated outcomes in specific study subgroups. Atezolizumab 1200 mg was administered intravenously every 3 weeks until loss of clinical benefit, unacceptable toxicity, death, consent withdrawal, decision to discontinue, commercial availability, or study closure. Response Evaluation Criteria in Solid Tumors V.1.1 responses and safety were evaluated by baseline renal function and histology. Objective responses occurred in 0/6 (0%), 4/19 (21%), 1/27 (3.7%), and 12/62 (19%) of evaluable patients with creatinine clearance (CrCl) <30, 30-45, 45-60, and ≥60 mL/min, respectively, and stable disease was seen in three patients with CrCl <30 mL/min. Objective responses were seen in 13/102 patients (13%) with urothelial carcinoma (UC) histology only and in 4/12 patients (33%) with UC with MVH. Treatment-related adverse event frequencies ranged from 35% to 54% across the earlier indicated CrCl subgroups and they were also similar in patients with pure UC or UC with MVH (46%). In this EAP mUC subgroup analysis, clinical benefit of atezolizumab occurred in patients with compromised renal function or MVH UC tumors. Safety was comparable across subgroups. We examined the efficacy and safety of atezolizumab for UC in certain patients participating in an EAP. We found that responses to atezolizumab occurred, and safety was similar, in most patient subgroups with varying levels of kidney functioning or less common types of tumor tissue histology.

Dataset Information

Efficacy and safety data in elderly patients with metastatic renal cell carcinoma included in the nivolumab Expanded Access Program (EAP) in Italy.

Publications

Efficacy and safety data in elderly patients with metastatic renal cell carcinoma included in the nivolumab Expanded Access Program (EAP) in Italy.

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