463 Background: Unclassified or not otherwise specified (NOS) renal cell carcinoma (RCC) is a rare and heterogeneous subtype, representing 2-6% of RCC cases PMID: 30510921. It is associated with poor prognosis, and prospective clinical trial data to guide treatment (Rx) decisions are limited. Herein, we aimed to assess Rx patterns and survival outcomes in pts with metastatic NOS RCC in a large real-world database. Methods: We utilized the US-based, electronic health record-derived deidentified Flatiron Health Research Database. Eligibility: diagnosis of NOS RCC with metastasis and receipt of first-line (1L) systemic Rx. Rx types from 1L to 5L are summarized using frequency and percentages. Real-world time to next therapy (rwTTNT) was defined as time from each line initiation to the next line of Rx or death and censored at the lost to follow-up. Real-world overall survival (rwOS) was defined as time from each line initiation to death and censored at the lost to follow-up. Kaplan-Meier method was used to estimate median rwTTNT and rwOS, and their 95% confidence intervals (CIs). Results: Among 13,909 pts diagnosed with metastatic RCC in the dataset, 2,589 had metastatic NOS RCC, of whom 1,718 received 1L Rx and were eligible and included in our analysis. Pts initiated 1L Rx between 2/4/2011 - 10/25/2024. Median age was 68 years (IQR 60 – 76), 69% were male, and 60% were White non-Hispanic. Of these, 43% received 2L Rx and 19% received 3L. In 1L, tyrosine kinase inhibitors (TKIs) were most commonly used (48%), followed by PD-1 inhibitor (PD-1i)-based regimens (CTLA-4i + PD-1i, 18%; PD-1i + TKI, 13%) and single-agent PD-1i (9%). In 2L, TKIs remained the most common (35%), followed by single-agent PD-1i (24%) and PD-1i-based combinations (CTLA-4i + PD-1i, 4%; PD-1i + TKI, 13%). In 3L, TKIs were again most commonly used (46%), followed by single-agent PD-1i (16%). Median rwTTNT and rwOS by Rx and line of Rx are summarized in Table. Conclusions: In this large real-world study, significant attrition with each line of Rx was observed. TKIs were the most common Rx across all lines. Survival outcomes remained poor across all regimens. These data highlight the urgent need for more effective therapeutic strategies to guide Rx in pts with metastatic NOS RCC. Median rwTTNT (mo, 95% CI) and rwOS (mo, 95% CI) by Rx and line of Rx in pts with metastatic NOS RCC. Rx 1LMedian rwTTNTn = 1718 1LMedian rwOSn = 1718 2LMedian rwTTNTn = 745 2LMedian rwOSn = 745 3LMedian rwTTNTn = 325 3LMedian rwOSn = 325 TKI 6.1 (5.3–6.8) 14 (12–16) 5.1 (4.5–6.8) 10 (7.9–14) 4.8 (3.6–5.7) 9.7 (7.5–13) CTLA-4i + PD-1i 5.5 (4.7–7) 14 (12–19) 4.2 (3.5–NR) 8.8 (7.1–NR) 4.7 (3.7–NR) 12 (8.8–NR) PD-1i + TKI 8.5 (6.7–10) 12 (11–17) 9.7 (7.2–13) 16 (13–20) 4.3 (3.4–12) 11 (6.2–16) PD-1i 3.9 (2.9–5.5) 9.8 (7.9–13) 5.3 (4.3–7.1) 12 (9.2–18) 7.7 (4.2–17) 11 (4.9–30) Everolimus 3.4 (1.9–9.7) 11 (5.9–20) 4.4 (3.7–6.1) 10 (6.2–18) 5.6 (4–NR) 16 (4.1–NR) i: inhibitor, NR: not reached.
Nandakumar et al. (Sun,) studied this question.