Attrition Rates in Metastatic Renal Cell Carcinoma (mRCC) Following First Line Immunotherapy-Based Treatment: Results...

Attrition rates for patients with mRCC are not well characterized in the era of immunoncology (IO)-based combinations. This study aims to quantify real-world attrition rates by line of therapy, analyze associated clinical predictors, and describe treatment sequencing across multiple international centers.

IMDC data for patients with mRCC who received first line Nivolumab + Ipilimumab (IO-IO) or IO- Vascular Endothelial Growth Factor receptor targeted therapy (VEGFR TT) (IO-VE) were included. Clinical and pathologic characteristics and outcomes were extracted. Chi-square tests were used to compare categorical variables between patients who received second line and those who did not. A logistic regression model was used to assess predictors of second line therapy initiation.

A total of 1411 patients were identified, of whom 995 patients were treated with first line IO-IO and 434 with IO-VE. Of them, 935 (704 first line IO-IO and 231 first line IO-VE) stopped first line and were suitable for second line therapy. Reasons for stopping first line included progressive disease (PD) in 41.1%, toxicity in 24.4%, death in 3.9%, complete response in 1.5% and other in 28.3%. Among second line suitable patients, 544 (58.2%) started any second line whereas 391 (41.8%) did not. Patients who stopped first line for PD were more likely to initiate second line than those who stopped for other reasons (57.9% vs. 17.6%, P < .00001). Patients who received second line were more likely to have clear-cell histology (77.2% vs. 66.8%, P = .04), without sarcomatoid features (57.2 vs. 44.8%, P = .02), a Karnofsky performance score (KPS) of 80 or higher (80.1 vs. 73.9%, P = .01), and bone metastases (39.0 vs. 28.1%, P = .0009). (Table 2). After adjusting for IMDC criteria, only age and reason for stopping first line remained significant predictors of receiving second line therapy. Among 353 patients who stopped second line, 199 (56.4%, overall 21.3%) started third line therapy. Of the 139 patients who stopped third line, 80 (57.6%, overall 8.6%) started fourth line therapy.

In this real-world analysis, we found that just over half of suitable patients received the subsequent line of therapy post first line. We were able to identify age and reason for stopping first line as predictors of second line therapy initiation.