Compassionate Use Program of Ipilimumab and Nivolumab in Intermediate or Poor Risk Metastatic Renal Cell Carcinoma: A Large Multicenter Italian Study

SIMPLE SUMMARY: Ipilimumab and Nivolumab (IPI-NIVO) improved survival in a pivotal phase III trial conducted in patients with metastatic Renal Cell Carcinoma (mRCC) with intermediate or poor International Metastatic RCC Database Consortium (IMDC) score when compared to sunitinib. A compassionate use program of IPI-NIVO was launched in Italy from April through October 2019. The aim of our retrospective study was to assess the outcome of mRCC patients treated with IPI-NIVO within the Italian compassionate use program. Despite one third of patients not completing the induction phase of IPI-NIVO due to either toxicity or early progression, the 12-month survival rate of 66.8% confirms that IPI-NIVO combination is an effective first-line regimen for mRCC patients with IMDC intermediate-poor risk score. ABSTRACT: This is a retrospective analysis on the safety and activity of compassionate Ipilimumab and Nivolumab (IPI-NIVO) administered to patients with metastatic Renal Cell Carcinoma (mRCC) with intermediate or poor International Metastatic RCC Database Consortium (IMDC) score as a first-line regimen. IPI was infused at 1 mg/kg in combination with Nivolumab 3 mg/kg every three weeks for four doses, followed by maintenance Nivolumab (240 or 480 mg flat dose every two or four weeks, respectively) until disease progression or unacceptable toxicity. A total of 324 patients started IPI-NIVO at 86 Italian centers. Median age was 62 years, 68.2% IMDC intermediate risk. Primary tumor had been removed in 65.1% of patients. Two hundred and twenty patients (67.9%) completed the four IPI-NIVO doses. Investigator-assessed overall response rate was 37.6% (2.8% complete). Twelve-month survival rate was 66.8%, median progression-free survival was 8.3 months. Grade 3 or 4 treatment-related adverse events occurred in 67 patients (26.9%). IMDC intermediate risk, nephrectomy, BMI ≥ 25 kg/m(2), and steroid use for toxicities correlated with improved survival, while age < 70 years did not. IPI-NIVO combination is a feasible and effective regimen for the first-line treatment of intermediate-poor IMDC risk mRCC patients in routine clinical practice.