Clinical trial exclusion criteria may lead to lack of evidence in real-world patients: how do the excluded fare?

In a study reviewing data from patients that would otherwise be excluded from clinical trials, no difference was found in overall survival (OS) in patients with hypertension versus patients without hypertension receiving systemic therapy for metastatic renal cell carcinoma (mRCC). Further studies are indicated to analyse responses of patients with hypertension.

Clinical trial exclusion criteria often include conditions commonly seen in real-world patients, such as autoimmune disease, cardiovascular conditions, and uncontrolled hypertension. As a result, while clinical trial outcomes often demonstrate favourable responses in participants who meet the inclusion criteria as delineated, there is a paucity of research that evaluates whether these favourable results will extend to real-world patients who were precluded from trial participation by the exclusion criteria.

In the current analysis, Dr Diana Maslov (Ochsner Health System, Louisiana, USA) and colleagues retrospectively reviewed data from trials that allowed patients with hypertension to participate [1]. Identified were patients with mRCC who had participated in clinical trials investigating target therapies for mRCC (most commonly tyrosine kinase inhibitors [TKIs]) that did not exclude patients with hypertension. Patient characteristics, treatment type, and response to treatment (using Response Evaluation Criteria in Solid Tumours version 1.1) were analysed. Furthermore, a list of common clinical trial exclusion criteria was compiled, such as hypertension, heart, liver or renal failure, and presence of autoimmune disease.

Of the 198 patients, 142 (71.72%) had a history of uncontrolled hypertension. Most patients (n=154, 77.8%) received single TKIs; specifically, 84 received pazopanib (42.4%), 43 received sunitinib (13.6%), and 27 received cabozantinib (13.6%). The remaining 44 patients (22.2%) underwent combination therapy; specifically, 21 received axitinib plus pembrolizumab (10.6%) and 23 received ipilimumab plus nivolumab (11.6%). The median duration of therapy was 5.17 months.

The analysis for survival included 165 (83.3%) of the patients; OS was not significantly affected by a history of hypertension (P=0.38; see Figure). The median OS for patients with hypertension was 15.90 months compared with 27.80 months for patients without hypertension, yielding an OS for all patients of 22.80 months.

Figure: OS in patients with and without hypertension [1]



Similarly, there was no difference in response rate between patients with hypertension versus patients without hypertension (P=0.65). Finally, there was no difference in progression-free survival between those participants who had a history of hypertension and those who did not (P=0.97).

The investigators call for more and larger studies to analyse the effects in more recently approved therapies for mRCC in real-world practice.

1. Maslov D. The impact of hypertension on response rates in patients with renal cell carcinoma. Abstract 287, ASCO Genitourinary Cancers Symposium, 11–13 February 2021.

 

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Posted on 24 March 202118 June 2021