Wong, Risa Liang

385 Background: Tyrosine kinase inhibitors (TKI) and immuno-oncology (IO) agents alone or in combination have revolutionized the landscape of management for untreated metastatic renal cell carcinoma (mRCC). Baseline quality of life (QOL) outside of interventional clinical trials and rationale for management decisions in mRCC are poorly understood. Methods: In this prospective observational study of 800 mRCC pts in the US, pts must: have a diagnosis of mRCC (any histology) with no prior systemic therapy (ST) for mRCC; be age ≥19 at informed consent; be able to comply with completion of PROs. Exclusion criteria include being treated for active malignancy other than mRCC or not intending to follow up at a study site within PCORnet. Pts undergo consent and baseline assessments by the study site team, with subsequent follow up by the central coordinating center. The primary objective is to determine distinct patterns of change in QOL and symptom burden of mRCC pts. A key secondary objective is to identify patterns of clinical management in the real world setting of mRCC across treatment regimens. Minimally important differences are defined as 3- and 7-points for FKSI-19 and FACT-G respectively. ClinicalTrials.gov ID: NCT04919122. Results: As of 9/1/2023, 173 pts have been enrolled (126 ST, 47 no ST [NST]): 75% male, 87% white, 73% clear cell, 52% intermediate risk and 47% poor risk. 47% had radical nephrectomy and 22% another solid tumor. ST pts as compared to NST pts were more likely to be poor risk (52% vs 16%); but differences in baseline pain were not significant. Of ST pts, 44 were treated with IO-IO (ipilimumab + nivolumab), 50 with IO-TKI (cabozantinib + nivolumab 38%, axitinib + pembrolizumab 38%, lenvatinib + pembrolizumab 24%) and 32 other (IO alone 34%, TKI alone 31%, investigational drug 25%). Reasons for NST included active surveillance (AS, 50%), other (21%), local therapy (13%). Mean differences between ST and NST for baseline FKSI-19 and FACT-G were 5.7 (95% CI: 1.2 – 10.2) and 3.3 (-2.6 – 9.3). There were no differences in pain or PROs between IO-IO and IO-TKI pts. Mean differences in FKSI-19 and FACT-G between AS vs IO-IO were 10.6 (4.8 – 16.4) and 8.6 (1.1 – 16.0); and vs IO-TKI were 11.0 (4.9 – 17.0) and 10.3 (3.5 – 17.1). On physician surveys, primary reasons for treatment selection were (in order of % selected): complete response (CR), prolonged survival (OS), prognostic factors (Px), treatment-free interval for IO-IO; versus delaying progression (PFS), OS, CR, Px for IO-TKI. Conclusions: Our data suggest differences in baseline QoL in pts treated with ST vs NST, as well as AS vs IO-IO or IO-TKI, in the real world. Reasons for selection of ST regimen differed among combination regimen classes. Completion of ODYSSEY will clarify baseline and longitudinal differences in pain and PROs among management strategies and give novel insights into the rationale for real world management of untreated pts with mRCC. Clinical trial information: NCT04919122 .

TPS739 Background: The landscape for treatment of metastatic renal cell carcinoma (mRCC) has changed dramatically over the past 7 years with the approvals of tyrosine kinase inhibitors and immune-oncology (IO) agents alone or in combination for untreated mRCC. However, multiple knowledge gaps remain. While active surveillance remains an option for selected pts, prospective evidence on selection of and outcomes for pts is limited. Recent phase III trials all used a common comparator, sunitinib, so no comparative effectiveness data on the new IO-based regimens exists. There are also no routinely used predictive biomarkers in mRCC pt management. Therefore, a better understanding of the biologic determinants associated with cancer heterogeneity and clinical outcomes through blood, tumor, and radiographic based assessments is needed. Importantly, longitudinal changes in health-related quality of life (QOL) and symptom burden of patients with mRCC initiated on new IO–based regimens outside of an interventional clinical trial are poorly understood. Pt reported outcomes (PRO) are rarely captured in a systematic manner. Addressing the evidence gap for how real world pts symptomatically change with treatment combinations and sequences over time is a pressing unmet need. Methods: This is a prospective, observational cohort, phase IV study of 800 mRCC pts in the US. Pts must: be age ≥19 at informed consent; have a diagnosis of mRCC (any histology) with no prior systemic therapy for mRCC (surgery and radiation therapy, prior neoadjuvant/adjuvant therapy for non-mRCC, and pts currently not on systemic therapy and being observed are all permitted); and be able to comply with completion of PROs. Those being treated for active malignancies other than mRCC or not intending to undergo follow up care at a study site within PCORnet are excluded. Pts will undergo consent and baseline assessments, including research blood collection and processing, by the study site team. A novel aspect of this study is the use of PCORnet and Medicare data to minimize data collection burden on sites. PCORnet, the National Patient-Centered Clinical Research Network, is a network of networks that curates EHR data from multiple health systems using a common data model. This allows subsequent follow up to be centrally coordinated by the coordinating center. PRO will be collected at baseline (pre-treatment), every 3 mos for 2 yrs, and then every 6 mos until end of follow up (minimum 18 mos follow-up; maximum 36 mos follow-up). The primary objective is to determine distinct patterns of change in QOL and symptom burden of mRCC pts receiving therapy. Secondary objectives include quantifying the time to treatment discontinuation of pts, identifying patterns of clinical management in the real world setting of mRCC pts on various treatment regimens, and evaluating overall survival of mRCC pts. ClinicalTrials.gov Identifier: NCT04919122 Clinical trial information: NCT04919122 .