Extended-Interval vs Standard-Interval Dosing of Single-Agent Pembrolizumab

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In a retrospective cohort study performed in U.S. veterans reported in JAMA Oncology, Strohbehn et al found that a minority of patients receiving singe-agent pembrolizumab for cancer received the extended-interval dosing of 400 mg every 6 weeks. Analysis of efficacy measured as the time to treatment discontinuation showed no difference between extended-interval vs standard-interval dosing.

As stated by the investigators: “Extended-interval dosing of pembrolizumab (400 mg every 6 weeks) was approved by U.S. Food and Drug Administration in April 2020 as an alternative to standard-interval dosing (200 mg every 3 weeks). Extended-interval dosing may enhance access, alleviate patient and health system financial toxicity, and improve patient quality of life, particularly during the COVID-19 pandemic. Neither adoption nor effectiveness of extended-interval [dosing] in the U.S. has been adequately described.”

Study Details

The study involved data from the Veterans Health Administration (VHA) on veterans who were prescribed single-agent pembrolizumab within the VHA between April 1, 2020, and July 1, 2021. Patients receiving a combination of pembrolizumab with cytotoxic chemotherapy or tyrosine kinase inhibitors were excluded.

Key Findings

A total of 835 veterans initiated single-agent pembrolizumab during the study period. Of these patients, 234 had non–small cell lung cancer (NSCLC).

Extended-interval dosing adoption increased steadily to 32.6% by January 2021, with this rate being maintained through August 2021. Use of extended-interval dosing for first pembrolizumab doses reached peak adoption in June 2020 and remained at a steady use rate of approximately 20% to 25% of prescriptions from November 2020 onward.

Among patients who began treatment with standard-interval dosing, 65% continued with it for the entire treatment duration. Among those who began with extended-interval dosing, 95% to 100% continued with it for the entire duration of treatment.

Among all patients, the median time to treatment discontinuation was 127.5 days for standard-interval dosing vs 168 days for extended-interval dosing (hazard ratio [HR] = 1.00, 95% confidence interval [CI] = 1.00–1.00, P = .08).

Among the 234 patients with NSCLC, 77.4% received standard-interval dosing and 22.6% received extended-interval dosing alone. The median time to treatment discontinuation was 112 days for standard-interval dosing vs 170 days for extended-interval dosing (HR = 1.00, 95% CI = 1.00–1.00, P = .15).

The investigators concluded: “This retrospective cohort study found that extended-interval dosing comprised a minority of single-agent pembrolizumab prescriptions despite the FDA approval and its potential health system and public health benefits. The findings support the time to treatment discontinuation equivalence of standard- and extended-interval pembrolizumab across indications, complementing clinical pharmacology and single-arm clinical trial data in melanoma. This study provides further support for extended-interval pembrolizumab dosing.”

Garth W. Strohbehn, MD, MPhil, of the VA Center for Clinical Management Research, University of Michigan, Ann Arbor, is the corresponding author of the JAMA Oncology article.

Disclosure: This study was funded by the VA National Oncology Program. For full disclosures of the study authors, visit

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.