Patients With Sarcomatoid Metastatic nccRCC May Benefit From IO Combination Regimens

The largest analysis to date of outcomes for patients with sarcomatoid and/or rhabdoid (S/R) metastatic non-clear cell renal cell carcinoma (nccRCC) treated with immunotherapy (IO)-based regimens will be presented at the American Society of Clinical Oncology 2023 Annual Meeting.

Patients with advanced RCC with S/R characteristics are at risk of poor clinical outcomes. Prior research has shown that IO-based combination therapies are associated with substantial efficacy for patients with metastatic S/R clear cell RCC compared with vascular endothelial growth factor-targeted therapy (VEGF-TT). Additionally, recent trials have shown promising activity of IO-based regimens in patients with advanced nccRCC, though further analysis is needed to determine the efficacy of IO regimens among patients with S/R nccRCC.

Chris Labaki, MD, and colleagues designed a study to analyze the effects of first-line IO regimens (IO plus IO or IO plus VEGF-TT) or first-line VEGF-TT monotherapy in patients with advanced nccRCC. A total of 103 patients with S/R nccRCC were included, of whom 32% (n=33) received first-line IO regimens. The primary outcomes were overall survival (OS) and time to treatment failure (TTF), and overall response rate (ORR) was a secondary outcome.

Researchers noted that OS and TTF were compared between the IO and VEGF-TT groups through Cox regression models adjusted for age, International mRCC Database Consortium risk groups, and nccRCC subtypes. ORR was compared between the groups through logistic regression adjusted for the same confounders.

After a median follow-up of 31 months, researchers found that patients with S/R nccRCC treated with IO regimens had significantly improved survival outcomes versus those receiving VEGF-TT (median OS, not reached vs 7.1; median TTF, 9.4 vs 2.9 months). A higher ORR was also noted in patients with S/R nccRCC receiving IO regimens (34.1% vs 10.9%, respectively).

Furthermore, researchers reported that among the 430 patients with non-S/R nccRCC—44 of whom were receiving IO regimens—no significant differences in survival outcomes were seen between regimen classes.

“Patients with S/R nccRCC appear to derive a substantial and selective benefit from IO regimens [compared with VEGF-TT],” study authors concluded. “These data support the use of IO-based regimens in patients with S/R nccRCC.”