Are there circumstances where you would recommend every 6 week dosing schedule for pembrolizumab monotherapy?

I am considering every 6 week pembrolizumab dosing in patients >70 years old in whom I want to reduce clinic visits for, especially in the context of the COVID-19 pandemic. This schedule was approved in Europe based on modeling/simulation (https://ascopubs.org/doi/abs/10.1200/JCO.2018.36.15_suppl.3062), but the FDA rejected the every 6 week dosing in February 2020.

3 Answers

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Medical Oncology · Cleveland Clinic

Answered on

FDA approval for q 6 week dosing of pembrolizumab is awaited but has yet to occur; this would represent a welcome change for our patients, as just happened with the recent approval of q 4 week dosing of atezolizumab.

Without FDA approval we are not using pembrolizumab 6 week dosing at this time, and this has been discussed with our oncology pharmacy colleagues. While it is expected that this may be a safe dosing schedule, an unfortunate reality is that payor reimbursement could be an issue and may result in increased cost to our patients. If a patient has concerns about on-site treatment during the pandemic, we have reassured them regarding our screening and sanitization procedures. as well as caregiver PPE use in the clinic and infusion areas. We do feel that it is safe to maintain our patients on their current treatment schedules, and have not noted any internal evidence for SARS-CoV-2 transmission from caregiver to patient or vice versa. If a patient receiving pembrolizumab still voiced concern regarding a visit and wished to cancel, that cycle would be deleted and we would plan to resume 3 weeks later if the patient was comfortable with a clinic visit at that time. I have little concern for loss of efficacy if a cycle is missed for such a reason.

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Medical Oncology · Donald and Barbara Zucker School of Medicine at Hofstra/Northwell

Answered on

Based on exposure-response evaluation using modeling and simulation data (ASCO 2018), I feel comfortable spacing out treatment to every 6 weeks in the current COVID crisis, particularly in elderly patients who have been on the agent for a while with excellent response and minimal disease burden.

However, since FDA rejected Merck's application for Q6W dosing (despite approval in Europe), I am often using 200 mg Q6W to avoid above-mentioned concerns for insurance rejections after detailed discussion with patients (and upon mutual written agreement). A post-pandemic retrospective analysis through multi-institutional collaboration would be very helpful to assess real world experience with this schedule.

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Medical Oncology · University of Maryland

Answered on · Updated on

I still favor 3-weekly pembrolizumab in the following situations:

1. During the induction of chemo-immunotherapy.

2. In maintenance phase with pemetrexed-pembrolizumab combination for adenocarcinoma.

3. When there is a concern of toxicity and I need to follow closely.

6-weekly 400 mg pembrolizumab have similar predicted exposures when compared with 3-weekly 200 mg (https://ascopubs.org/doi/abs/10.1200/JCO.2018.36.15_suppl.3062).

400 mg 6-weekly dose is now approved by the FDA (https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-new-dosing-regimen-pembrolizumab#:~:text=On%20April%2028%2C%202020%2C%20the,every%20three%20weeks%20dosing%20regimen.)

Personally, I recommend 6 weekly pembrolizumab to those patients

> whose disease had response in the most recent scan and the next interval scan is planned in 3 months time,

> is on single agent maintenance pembrolizumab and,

> who has not experienced any significant immune-related adverse events.