Extended-interval dosing with pembrolizumab is similar to standard-interval dosing

1. No difference in time-to-treatment discontinuation noted between standard-dosing and extended-interval dosing

2. Immune-related adverse events were not dissimilar between groups, as represented by prescriptions for levothyroxine and prednisone

Evidence Rating Level: 2 (Good)

Study Rundown: Pembrolizumab, an immune checkpoint inhibitor, is the standard treatment for many cancers. Standard dosing of this medication is 200mg every 3 weeks. Delivery of 400 mg every 6 weeks as an extended-dosing regimen was approved in April 2020 by the Food and Drug Administration (FDA) of the United States. This study compared the effectiveness of the extended-dosing regimen to the standard-interval dosing. Data from two cohorts were examined: a cohort comprised of all patients (all-diseases) and a sub-cohort comprised of patients with non-small cell lung cancer (NSCLC). The primary outcomes of this study were the number and proportion of prescriptions for the new extended-regimen as well as time-to-treatment discontinuation (TTD). TTD is measured from the first prescription to the end of the most recent prescription. Secondary outcomes included adverse events (AEs) that were immune-related. These were assessed indirectly via prescriptions for prednisone and levothyroxine. The adoption of the extended regimen of pembrolizumab reached 32.6% from April 2020 to January 2021 and remained there until August 2021. Between 95-100% of patients who were started on extended-interval dosing continued with it for the duration of their treatment, compared to only 65% of patients who started standard-dosing who remained with that treatment. In both cohorts, there were more patients provided with standard-interval regimens and TTD similar between both regimens. Adverse events were similar between treatment regimens in either cohort. Limitations to this study include the relative lack of female patients in the cohorts. As such, the data should be applied to the general population with this in mind. Overall, the results from this study suggest extended-interval dosing of pembrolizumab may be more suitable as best-practice treatment as it is no less effective than standard treatment, does not result in more adverse events and is less of a strain to the healthcare system.

Click to read the study in JAMA Oncology

Relevant Reading: The drug-dosing conundrum in oncology—when less is more

In-Depth [retrospective cohort]: This retrospective cohort study was completed using data from the Veterans Health Administration (VHA). Two cohorts of patients were identified: the primary cohort consisting of all patients with all diseases and a sub-cohort consisting of patients with non-small cell lung cancer (NSCLC). There were 835 patients in the all-diseases cohort. Standard-interval dosing was provided to 81.0% of these patients and extended-interval dosing was given to 19.0%. TTD for standard-interval dosing was 127.5 days as compared to 168 days for extended-interval dosing (hazard ratio (HR), 1.00; 95% confidence interval (CI), 1.00-1.00). For AE assessment, there were no differences between the groups for immune-reaction prescriptions. There were 234 patients with NSCLC. Of these, 77.4% were given standard-interval dosing, 22.6% were given extended-interval dosing. For patients receiving standard-interval treatment, TTD was 112 days, compared to 170 days in the extended-interval treatment group (HR, 1.00; 95% CI, 1.00-1.00). There were no differences in AE as per prescriptions for immune-related reactions.

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