Clinical and Economic Impact of Early vs Delayed Progression After First-Line TKIs in Patients With Metastatic RCC

Early progression after first-line tyrosine kinase inhibitor (TKI) treatment for metastatic renal cell carcinoma (RCC) is associated with worse clinical outcomes and higher healthcare resource utilization and costs than delayed progression (J Manag Care Spec Pharm. 2021;1-11. doi:10.18553/jmcp.2021.20569).

“A key therapeutic goal of metastatic RCC treatment is delayed disease progression. The degree to which early therapeutic success affects downstream outcomes is not well established,” explained Thomas E Hutson, DO, PharmD, Texas Oncology Sammons Cancer Center, Dallas, TX, and colleagues.

This study aimed to evaluate the clinical and economic impact of early vs delayed disease progression after first-line therapy with TKIs in patients with metastatic RCC.

The US Veterans Health Administration database was used to identify patients with newly diagnosed metastatic RCC treated with a TKI in the first-line setting and who progressed to second-line therapy between October 2013 and March 2018. Patients were categorized by median time from initiation of first-line therapy to initiation of second-line therapy into early and delayed progression cohorts.

Researchers assessed clinical outcomes, including time to second-line therapy discontinuation, time to third-line treatment initiation, and overall survival (OS). In addition, HCRU and costs were compared between cohorts.

Kaplan-Meier curves were used to estimate median time to discontinuation, time to next line of treatment, and time to death for each cohort. Multivariate analysis was used to adjust for the influence of differences in cohort characteristics. Cox proportional hazards models were used to assess the impact of predictive factors on clinical outcomes.

A total of 289 patients were included in the analysis and stratifies as early (n = 145) or delayed progression (n = 144). Baseline characteristics were similar between the two cohorts.

Median time from first-line therapy initiation to second-line therapy discontinuation was 7.9 months in the early progression cohort vs 18 months in the delayed progression cohort. Median time from first-line therapy initiation to third-line therapy initiation was 9.4 months and 21.8 months, respectively.

In addition, median OS was 19.7 months in the early progression cohort vs 36.4 months in the delayed progression cohort.

Descriptive analysis suggested lower risks for second-line therapy discontinuation (HR = 0.40, 95% CI = 0.31-0.52), third-line therapy initiation (HR = 0.42, 95% CI = 0.32-0.55), and death (HR = 0.46, 95% CI = 0.33-0.64) for those with delayed progression.

After adjusting for possible confounding factors, comparative analysis showed median all-cause hospital length of stay was .4 days in the delayed progression cohort vs .8 days for early progression (P = .0004). In addition, delayed progression was associated with fewer pharmacy visits (3.57 vs 4.08 visits; P = .0266) and lower total healthcare costs ($10,342 vs $13,388; P = .0347) per patient per month.

“In patients with [metastatic] RCC, early progression after 1L [first-line] therapy initiation is associated with generally worse clinical outcomes and statistically significantly greater healthcare resource utilization and costs than delayed progression,” concluded Dr Hutson and colleagues.

“This finding highlights the importance of initiating therapy with an optimal 1L treatment regimen that has been proven to delay disease progression,” they added.—Janelle Bradley