Use of targeted therapies for advanced renal cell carcinoma in the Veterans Health Administration

Abstract

Background The objective of this study is to describe the use of targeted therapies for the treatment of advanced renal cell carcinoma (RCC) and overall survival (OS) among patients in clinical practice in the Veterans Health Administration (VHA). Methods A retrospective cohort of 286 patients from 24 VHA Medical Centers diagnosed with advanced clear cell RCC between Fiscal Year (FY) 2010 and FY2014 was followed through September 30, 2016. Among patients who received targeted therapy, we described the medications taken, duration of therapy, and overall survival. We also assessed the effect of the first therapy received on overall survival using Cox Proportional Hazards models. Results There were 66 patients who did not receive therapy for their advanced RCC. Of the 220 treated patients, the mean (sd) number of medications received was 1.9 (1.1). The medications most commonly used first were sunitinib (61.8%), pazopanib (17.3%), and temsirolimus (10.9%). The median duration of first‐line therapy was 86 days (interquartile range [IQR] 42, 210). Median total duration of therapy was 159 days (IQR 58, 397). 62.3% of patients had ≥ 1 dose of therapy held or reduced, mainly due to an adverse drug event (ADE). Median survival from the start of treatment to death was 1.08 years (IQR 0.80, 1.31). Finally, receipt of temsirolimus vs sunitinib (HR 1.95 [95%CI 1.09,3.47]) as the first targeted therapy was independently associated with an increased hazard of death. Conclusion Our analysis of targeted therapies for advanced RCC in VHA suggests duration of treatment is shorter in a real‐world setting than in clinical trials, and dose reductions and ADEs are more common.

Patterns of first-line targeted therapy utilization and adherence among older adults diagnosed with metastatic renal cell carcinoma

“…Contrastingly, in studies of a younger population from the Veterans Health Administration (VHA; average age 66.3 years) and a Medicare population with a similar age distribution to our cohort (median age group 70-79 years) 23.1% and 32.9% of patients with metastatic kidney cancer did not receive anticancer therapy, respectively [42,43]. The reason for these discrepancies is unclear; however, it may be attributable to previous studies identifying therapy use any time after diagnosis, or the exclusion of patients that actively progress to metastatic disease in our study [42].…”

“…The observed treatment duration of first-line oral targeted therapy was relatively short (median 71 days, IQR 40-132), and was in agreement with that observed from the VHA (86 days) [42]. While other studies have reported longer times to discontinuation, these often focused on individual drug types, or may reflect differing censoring criteria and younger study populations [16,18,20,21].…”

“…Previously poor performance and comorbidities were associated with receiving no therapy [41,42]. Similarly, we found evidence that increased comorbidity, frailty and age may be associated with decreased first-line therapy initiation.…”

Informing Patients About Expected Outcomes: The Efficacy-Effectiveness Gap

“…2 Examples of an EEG showing differences in survival between people with cancer who were treated in trials and those who were trial eligible are listed in Table 1. [3][4][5][6][7][8] Levels of toxicity also are lower in clinical trials: the relative rate of febrile neutropenia resulting from cytotoxic treatment was 74% higher in observational studies compared with rates from the same regimens tested in randomized clinical trials (RCTs). 9 The EEG also is evident in other fields of medicine.…”

Potential Cost Implications for All US Food and Drug Administration Oncology Drug Approvals in 2018

“…Prior work demonstrated that the duration of therapy for some anticancer drugs is shorter in the real-world compared with clinic trials, 17,18 and shorter courses of therapy would permit a greater degree of use for a given budgetary threshold. Lastly, determining some of the displaced therapies (mostly with single-arm studies) required judgment as practicing adult and pediatric hematologist-oncologists, and we erred toward more expensive comparators, thus lowering the estimated net cost of new approvals.…”