In recent years, prognostic classifications have been considered an area of growing interest in mRCC. However, independently from the classification used (Memorial Sloan Kettering versus Heng’s) the presence of brain, liver and bone metastases (mets) or sarcomatoid features (G4) resulted in a poorer outcome for pts with mRCC treated with targeted therapies (antiangiogenic agents or mTOR Inhibitors). Regarding this topic, the large Italian EAP represent an important opportunity to analyze the impact of nivolumab in pts treated in a daily clinical practice setting.
Nivolumab was available upon physician request for pts aged ≥18 years who relapsed after at least one prior systemic treatment in the advanced or metastatic setting. Nivolumab 3 mg/kg was administered intravenously every 2 weeks for a maximum of 24 months. Pts included in the analysis had received ≥ 1 dose of nivolumab and were monitored for adverse events (AEs) using Common Terminology Criteria for Adverse Events.
Of 389 Italian pts with mRCC enrolled in the EAP, 32 pts (8%) had brain mets, 128 (33%) had liver and 193 (50%) had bone mets. Baseline characteristic are described in the Table. These pts achieved a disease control rate (DCR) of 53%, 45% and 47% respectively. Six and 12 months overall survival rates in the 3 groups of mets were 87.0% and 66.8%, 75.6% and 62.0%, 78.0% and 58.9%, respectively. Histological grading, a matter of high interest, was assigned according to Fuhrman's classification: 51 pts had G4 tumor. The objective response rates in these pts and in the overall population were 23% and 22%, respectively, with a 6 and 12 months OS rate of 61% and 53.6% for the G4 group. The safety profile of the subgroups described above was in line with the general population.
These results suggest that also pts with poor prognostic factors may derive relevant benefits with nivolumab, with safety results consistent with previously reported data.Table:
|Age, median (range)||Brain Mets||Liver Mets||Bone Mets|
|65 (43-77)||65 (43-81)||65 (40-84)|
|ECOG PS %:||0 1 2 NA||41 50 6 3||42 50 7 1||39 48 10 3|
|Number of prior Therapies %:||1 2 3 > =4 NA||13 44 37 6 0||13 37 24 24 2||14 36 30 19 1|
Clinical trial identification
Expanded Access Program
Legal entity responsible for the study
Italian RCC EAP Group
S. Bracarda: Advisory Board Member for Pfizer, Novartis, Bristol-Myers Squib, Exelixis, Ipsen, Roche, Genentech, Eusa Pharma. PI for clinical studies with Bristol-Myers Squib, Pfizer, Roche, Exelixis. L. Galli: Advisory Board for Pfizer, Novartis. U. De Giorgi: Advisory Board for Bristol-Myers Squib, Pfizer, Novartis, Ipsen, Astellas, Janssen, Sanofi. G. Procopio, C. Porta: Advisory Board for Bristol-Myers Squib, Pfizer, Novartis, Ipsen. E. Cortesi: Advisory Board for Bristol-Myers Squib, Pfizer, Ipsen. All other authors have declared no conflicts of interest.