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Comparative Study
. 2021 May 3;4(5):e2111329.
doi: 10.1001/jamanetworkopen.2021.11329.

Real-World Survival Outcomes Associated With First-Line Immunotherapy, Targeted Therapy, and Combination Therapy for Metastatic Clear Cell Renal Cell Carcinoma

Nicholas H Chakiryan  1 , Da David Jiang  2 , Kyle A Gillis  3 , Elizabeth Green  1 , Ali Hajiran  1 , Lee Hugar  1 , Logan Zemp  1 , Jingsong Zhang  1 , Rohit K Jain  1 , Jad Chahoud  1 , Philippe E Spiess  1 , Wade Sexton  1 , Scott M Gilbert  1 , Brandon J Manley  1
Affiliations
Comparative Study

Real-World Survival Outcomes Associated With First-Line Immunotherapy, Targeted Therapy, and Combination Therapy for Metastatic Clear Cell Renal Cell Carcinoma

Nicholas H Chakiryan et al. JAMA Netw Open. .

Abstract

Importance: Clinical trials have shown an overall survival (OS) benefit associated with first-line immunotherapy (IT) and combination targeted therapy (TT) and IT regimens compared with TT among patients with metastatic clear cell renal cell carcinoma (RCC). Generalizability of these findings in a real-world cohort outside of a clinical trial setting is unclear.

Objective: To assess the association of first-line TT, IT, and combination TT and IT regimens with OS in a real-world cohort of patients with metastatic clear cell RCC.

Design, setting, and participants: This retrospective propensity-matched cohort study identified 5872 patients with metastatic clear cell RCC in the National Cancer Database from January 1, 2015, to December 31, 2017, who received first-line TT, IT, or combination TT and IT and were not treated on a clinical trial protocol. Patients were stratified by first-line systemic treatment. Statistical analysis was conducted from October 1 to December 1, 2020.

Main outcomes and measures: The primary outcome was OS from the date of diagnosis to death or censoring at last follow-up. After 1:1:1 nearest-neighbor caliper matching of propensity scores, survival analyses were conducted using Cox proportional hazards regression and Kaplan-Meier estimates.

Results: The final study population included 5872 patients (TT group: n = 4755 [81%]; 3332 men [70%]; median age, 64 years [interquartile range, 57-71 years]; IT group: n = 638 [11%]; 475 men [74%]; median age, 61 years [interquartile range, 54-69 years]; and combination TT and IT group: n = 479 [8%]; 321 men [67%]; median age, 62 years [interquartile range, 55-69 years]), and the matched cohort included 1437 patients (479 per treatment group). Patients in the IT and combination TT and IT groups were younger than those in the TT group, had fewer comorbid conditions (Charlson-Deyo score of 0, 480 of 638 [75%] in the TT group, 356 of 479 [74%] in the IT group, and 3273 of 4755 [69%] in the combination TT and IT group), and were more often treated at academic centers (315 of 638 [49%], 216 of 479 [45%], and 1935 of 4755 [41%], respectively). Both first-line IT and combination TT and IT were associated with improved OS compared with first-line TT for patients with metastatic clear cell RCC (IT group: hazard ratio [HR], 0.60 [95% CI, 0.48-0.75]; P < .001; combination TT and IT group: HR, 0.74 [95% CI, 0.60-0.91]; P = .005). No survival difference was seen between the IT and combination TT and IT groups (combination TT and IT: HR, 1.24 [95% CI, 0.98-1.56]; P = .08).

Conclusions and relevance: This study suggests that both first-line IT and combination TT and IT were associated with improved OS compared with first-line TT for patients with metastatic clear cell RCC. These findings are similar to those identified in recently reported clinical trials, lending confidence to the broader applicability of these findings outside of a clinical trial setting.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Zhang reported receiving personal fees from Merck, Bayer, and AstraZeneca outside the submitted work. Dr Spiess reported serving as a National Comprehensive Cancer Network (NCCN) Bladder and Penile Cancer Panel member and vice-chair. Dr Manley reported serving as an NCCN Kidney Cancer Panel member. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Flow Diagram Detailing Selection of the Study Population
ccRCC indicates clear cell renal cell carcinoma; IT, immunotherapy; NCDB, National Cancer Data Base; and TT, targeted therapy.
Figure 2.
Figure 2.. Kaplan-Meier Estimates for Overall Survival, Stratified by Treatment Group
Log-rank P value reported within the figure. IT indicates immunotherapy; and TT, targeted therapy.
See this image and copyright information in PMC

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