The Intricacies of Discontinuation Rates With Pembrolizumab Across Cancer Types

Omid Hamid, MD, chief of Translational Research and Immunotherapy and director of the Melanoma Center and Phase I Immuno-Oncology Program at The Angeles Clinic and Research Institute, an affiliate of the Cedars Sinai Medical Center, stated that discontinuation of pembrolizumab (Keytruda) generally comes from higher-grade toxicities.

During a conversation with CancerNetwork®, Hamid spoke about a safety profile evaluation of pembrolizumab that he conducted.1 When it comes to discontinuations, adverse effects (AEs) like colitis, type 1 diabetes, myositis, myocarditis, or the neurological type are generally responsible.

As he noted, the discontinuation rate of pembrolizumab due to AEs is 12.7%, and at times, the rate can approach that of targeted agents or chemotherapeutics. One of the things he highlighted as important is communicating with the patient regarding what types of AEs they might deal with and the frequency of discontinuation.

Transcript:

You need to begin to talk to them about the fact that these toxicities are different than what we are used to with targeted [therapy] or chemotherapy. You begin by saying that these are inflammatory, you describe the most common ones, and you set a baseline: “What’s your baseline? How is your skin normally? How are your bowel movements?” [These] are difficult discussions because they’re different. Then you begin to discuss the fact that these are novel toxicities that can happen anytime and usually don’t happen with the first one. The majority resolve, and they can happen anytime, not just the day after or the week after. At times, you’re sending people away for 6 weeks, and you create a network for them to call back, whether it’s a nurse, your team, or yourself. You also note that these can happen after discontinuation. Every visit should begin with a discussion about any changes [regarding AEs] and a review of what these toxicities are.

The majority of the discontinuations, in my experience, have to do with the higher-grade toxicities, whether they’re colitis or pneumonitis; the neurological ones, diabetes type 1, myositis, myocarditis, et cetera. They have to do with the fact that these toxicities, at times, don’t go back to baseline. It is, that’s not the most important thing.

Those are immune-related AEs. The majority of discontinuations do come from AEs that are not immune-related; they can be related to the drug or related to disease progression. What we see are discontinuation rates to AEs that are, at times, similar or higher [than] targeted agents and chemotherapeutics. When I talk to patients, I state that there are discontinuations; I relay that each patient is an individual case and that we will work to get them the most benefit, and that comes from the communication of AEs.

Reference

Brahmer JR, Long GV, Hamid O, et al. Safety profile of pembrolizumab monotherapy based on an aggregate safety evaluation of 8937 patients. Eur J Cancer. 2024;199:113530. doi:10.1016/j.ejca.2024.113530