Abstract Background Papillary renal cell carcinoma (pRCC) is the most common non-clear cell RCC subtype, yet prospective evidence guiding first-line systemic therapy remains limited. The phase 2 PAPMET trial in molecularly unselected pRCC and the phase 3 SAVOIR trial in MET-driven pRCC demonstrated clinical benefit, but neither showed overall survival improvement and were limited by small sample size (Pal et al., Lancet 2021; Choueiri et al., JAMA Oncol 2020). In this context, as IO-based combinations have gained traction in clinical practice following promising activity in single-arm studies, we leveraged real-world data (RWD) to characterize evolving treatment patterns and associated outcomes in pRCC. Methods Patients with pRCC were retrospectively identified from the ConcertAI Patient360™ RCC Dataset, a US-based de-identified, human curated comprehensive real-world dataset, generated from multiple electronic medical record systems and linked with medical and pharmacy claims as well as third party date of death information. Histology was defined by ICD-O-3 codes (8260/3, 8050/2, 8050/3, 8052/2, 8052/3, 8130/2, 8130/3) and NCI System codes (C27886, C27887), excluding clear cell papillary RCC (8323/1). Among patients with metastatic disease who received first-line systemic therapy, regimens were categorized as tyrosine kinase inhibitors (TKIs), IO (monotherapy or IO/IO), MET inhibitors (METi), mTOR inhibitors (mTORi), or IO-based combinations (IO/TKI or IO/METi). Temporal trends, demographics, and outcomes were assessed. Real-world PFS (rwPFS) and overall survival (rwOS) were estimated using Kaplan–Meier methods and compared across treatment groups. Cox models evaluated associations between treatment and survival with adjustment for clinical and demographic factors. Results Of 391 patients with pRCC, 385 (98.5%) had metastatic disease, of whom 216 (55.2%) initiated first-line systemic therapy between January 1, 2016, and May 1, 2024, and were included in the analyses. Median age was 65.6 years (IQR, 56.4–76.3), and 75.6% were male. Most were treated in community settings (89.4%). Patients were primarily White (61.0%) or Black/African American (26.0%); 5.5% were Hispanic or Latino. Most were from the South (40.3%), Midwest (16.1%), or Northeast (15.6%). TKIs were the most frequently used first-line regimen (49.5%), followed by IO (21.8%), METi (15.3%), IO/TKI or IO/METi (10.6%), and mTORi (2.8%). TKIs predominated from 2016 to 2019, after which IO and IO-based combinations became the most common first-line therapies. Median rwPFS was 5.4 months (95% CI, 4.07–7.06) for TKIs, 5.0 (2.52–6.30) for IO, 4.9 (2.95–8.93) for METi, 2.4 (1.80–12.74) for IO/TKI or IO/METi, and 2.0 (0.32–3.21) for mTORi. Median OS was 14.6 months (10.50–19.90) for TKIs, 18.7 (15.00–26.10) for IO, 14.8 (9.80–24.80) for METi, 9.3 (5.19–37.45) for IO/TKI or IO/METi, and 6.9 (0.32–11.10) for mTORi. Results were similar after adjustment for age, gender, race, geographic region, practice setting, stage at diagnosis, and ECOG. Conclusions In this national RWD cohort of metastatic pRCC, a shift toward IO and IO/TKI or IO/METi combinations was observed in recent years. However, survival outcomes remained similar across treatment groups. These findings underscore the need for phase 3 randomized trials. Ongoing studies such as STELLAR-304 (NCT05678673) and SAMETA (NCT03091192) reflect the current clinical equipoise and are essential to defining optimal first-line therapy in metastatic pRCC.
Zugman et al. (Wed,) studied this question.
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