Characterizing progression to subsequent lines of therapy in metastatic renal cell carcinoma (mRCC) after nivolumab plus ipilimumab (Nivo plus Ipi): Results from the International mRCC Database Consortium (IMDC).

4538 Background: Treatment patterns and number of lines of therapy for patients with mRCC are not well characterized in the era of immunoncology-based combinations. We aimed to quantify the attrition rates by line of therapy and to examine predictors of receiving second-line (2L) treatment. Methods: Using the IMDC, patients with mRCC who received first-line (1L) Nivo+Ipi were included. Clinical and pathologic characteristics and outcomes were extracted. Chi-square tests were used to compare categorical variables between patients who received 2L and those who did not. A logistic regression model was used to assess predictors of 2L therapy initiation in eligible patients. Results: 995 patients treated with 1L Nivo+Ipi were identified, of whom 704 stopped 1L and were thus eligible for 2L therapy. Reasons for stopping 1L included progressive disease (PD) in 39.5%, toxicity in 25.0%, death in 4.3%, complete response in 1.6% and other in 29.7%. Among 2L eligible patients, 410 (58.2%) received 2L whereas 294 (41.8%) did not. Patients who stopped 1L for PD were more likely to initiate 2L than those who stopped for other reasons (81.7% vs 43.0%, p <0.001). Patients who received 2L were more likely to have clear-cell histology (75.1 vs 62.9%, p=0.02), bone metastases (39.8 vs 29.6%, p=0.01), and only one site of metastases (18.3 vs 10.5%, p=0.01) and less likely to be poor risk by IMDC criteria (27.1 vs 34.4%, p=0.03). After adjusting for IMDC criteria, no predictors of receiving 2L therapy remained significant. The overall response rate to 1L therapy was lower in patients who received 2L than in those who did not: 18.5% (76/366) and 33.7% (99/245), respectively (p<0.001). Among 258 patients who stopped 2L, 145 (56.2%, overall 20.6%) started third-line (3L) therapy. Of the 98 patients who stopped 3L, 52 (53.1%, overall 7.4%) started fourth-line therapy. Conclusions: In our study, we found that over half of eligible patients received the subsequent line of therapy. We were unable to identify predictors of 2L therapy initiation. Attrition rates between lines of therapy have important implications for patient counseling, cost analyses, and clinical trial design. [Table: see text]