Comparative real-world survival outcomes of metastatic papillary and clear cell renal cell carcinoma treated with immunotherapy, targeted therapy, and combination therapy.

While there are a plethora of studies supporting novel treatment approaches in metastatic clear cell renal cell carcinoma (ccRCC), much of the data used to inform care of patients with metastatic papillary RCC (pRCC) is extrapolated from ccRCC. Several recent phase III trials have supported the use of immunotherapy (IO) and targeted therapy (TT)+IO in ccRCC, without corresponding data for pRCC. Using ccRCC as a comparison group, we sought to describe real-world trends in the utilization of systemic therapy and its impact on overall survival (OS) among patients with metastatic pRCC.

Using the National Cancer Database (NCDB), we identified cases of metastatic pRCC and ccRCC between 2015 and 2018. Patients were stratified into groups based on histology and first-line treatments (TT, IO, TT + IO). Differences in baseline characteristics were assessed using the Kruskal-Wallis test for continuous variables, and the Chi-square or Fisher's exact test for categorical variables. Survival analysis was performed using Kaplan-Meier estimates and multivariable Cox regression analyses.

A total of 6,920 patients with a diagnosis of metastatic RCC were identified: 594 (8.6%) with pRCC and 6,326 (91.4%) with ccRCC. Overall, 4,710 patients received TT (455 pRCC and 4,255 ccRCC), 1,585 received IO (77 pRCC and 1,508 ccRCC), and 625 received TT+IO (62 pRCC and 563 ccRCC). Temporal trend between 2015 and 2018 revealed an increased utilization of IO and TT + IO for pRCC and ccRCC. In patients with metastatic pRCC, neither IO (HR 1.03; 95% CI 0.75-1.42) nor TT+IO (HR 0.90, 95% CI 0.63-1.28) were associated with better OS compared to TT alone. In contrast, both IO and combination TT and IO were associated with significantly better OS than TT for patients with metastatic ccRCC (IO group: hazard ratio [HR] 0.75, 95% confidence interval [CI] 0.68-0.82; TT+IO group: HR 0.82, 95% CI 0.72-0.93). Cytoreductive nephrectomy was associated with better OS in both pRCC (HR 0.59, 95% CI 0.46-0.77) and ccRCC (HR 0.54, 95% CI 0.50-0.58).

Although IO and TT + IO were associated with better OS among patients with metastatic ccRCC, this same effect was not observed among patients with pRCC.

Urologic oncology. 2023 Jan 05 [Epub ahead of print]

Carlos Riveros, Sanjana Ranganathan, Jiaqiong Xu, Courtney Chang, Dharam Kaushik, Monica Morgan, Brian J Miles, Taliah Muhammad, Maryam Anis, Monty Aghazadeh, Jun Zhang, Eleni Efstathiou, Zachary Klaassen, Michael A Brooks, Brian Rini, Christopher J D Wallis, Raj Satkunasivam

Department of Urology, Houston Methodist Hospital, Houston, TX, USA., Center for Health Data Science and Analytics, Houston Methodist Hospital, Houston, TX, USA., Department of Urology, University of Texas Health, San Antonio, TX, USA., Department of Medical Oncology, Houston Methodist Hospital, Houston, TX, USA., Division of Urology, Medical College of Georgia, Augusta University, Augusta, GA, USA., Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA., Division of Urology and Surgical Oncology, Department of Surgery, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, Ontario, Canada; Division of Urology, University of Toronto, Toronto, Ontario, Canada; Division of Urology, Mount Sinai Hospital, Toronto, Ontario, Canada., Department of Urology, Houston Methodist Hospital, Houston, TX, USA. Electronic address: .