Impact of trial-eligibility as factor for clinical outcome of patients with renal cell carcinoma treated with first-line pazopanib: Subgroup analysis from the prospective, non-interventional study PAZOREAL.

e16511 Background: In a real-world setting, a substantial number of patients (pts) with metastatic renal cell carcinoma (mRCC) do not meet all eligibility criteria for a clinical trial. Thus, data on effectiveness and safety of 1st-line (1L) treatment with pazopanib (PAZO) as well as quality of life (QoL) is underrepresented for those pts and data on treatment sequences implementing PAZO as 1L are sparse. Methods: PAZOREAL is a prospective, multi-center, non-interventional study to evaluate effectiveness, safety and QoL in pts with mRCC treated with 1L PAZO, and nivolumab (NIVO) or everolimus in second and third line. In this subgroup analysis, the clinical outcome of trial-eligible (TE) and trial-ineligible (TIE) pts with mRCC was assessed by means of overall survival (OS), time on drug (ToD), treatment-emergent adverse events (TEAE) and QoL evaluated by EQ-5D-5L. Pts were rated TIE if they met at least one of the following three ‘TIE criteria’: (i) Karnofsky Performance Status < 70%, (ii) hemoglobin below the lower limit of normal, and (iii) non-clear cell carcinoma1. Results: Of 398 pts treated between December 2015 and February 2021, 376 pts received 1L treatment with PAZO. The median age was 69.7 years. 146 pts were categorized TE and 184 pts TIE, for 46 pts assessment was not applicable. Most of all pts were initially treated with PAZO 800 mg (TE: 71.9% vs TIE: 63.0%). Median ToD for PAZO was 7.7 months (95% CI 6.1-9.0) for TE and 6.0 months (95% CI 4.5-8.1) for TIE. A similar fraction of TE and TIE pts were treated with 2L NIVO (43.8% vs 44.0%). Median OS was 53.2 months (95% CI 38.9-NA) for TE and 26.0 months (95% CI 17.3-35.9) for TIE. The 12-month OS rate was 77.9% for TE and 67.1% for TIE. In patient reported outcome (PRO) measures, baseline QoL was estimated higher for TE than TIE, i.e., 63.2% TE vs 49.2% TIE pts had no limitations for mobility and 82.9% TE vs 61.7% TIE pts were independent in self-care. Frequency of related TEAEs grade 3/4 were comparable for TE and TIE (26.7% vs 25.0%), while TE tended to have less related serious TEAEs (13.0% vs 16.3%). Treatment was discontinued due to related TEAEs in 19.2% of TE and 13.0% of TIE pts. Conclusions: PAZOREAL provides real-world data for mRCC pts usually not represented in clinical trials during the study period. As it was to be expected, median OS and PRO were more favorable for TE than for the TIE pts, reflecting the difference in general condition between these groups. But more importantly, these data underline the tolerability of 1L PAZO treatment even for TIE pts, which is supported by comparable ToD for 1L PAZO and the comparable safety profile in both subgroups.1 Marschner, N. et al. Clin Genitourin Cancer 2017; 15(2):e209-215. doi:10.1016/j.clgc.2016.08.022.