Assessing Pembrolizumab AEs in Advanced mCRPC

May, 05, 2024 | Genitourinary Cancer, Prostate Cancer


  • The KEYNOTE-641 phase 3 trial aimed to assess AE’s of pembrolizumab in patients with mCRPC.
  • The primary endpoints were to determine PFS & OS.
  • Researchers noticed that Pembrolizumab in mCRPC exhibited manageable AEs, primarily fatigue, with a rare need for hospitalization or treatment discontinuation.

Prostate cancer represents the second most common cancer in men worldwide and is the fifth most common cause of cancer death in the United States. Among its advanced forms, castration-resistant prostate cancer (CRPC) poses significant challenges, particularly when it progresses to metastatic CRPC (mCRPC) and becomes unresponsive to hormonal therapy.

The phase-3 KEYNOTE-641 trial evaluated the efficacy of pembrolizumab in combination with hormonal therapy for patients with mCRPC. However, the trial was discontinued as pembrolizumab failed to achieve its primary endpoints of progression-free survival (PFS) and overall survival (OS).

Singla D and the team aimed to investigate the incidence and severity of adverse events (AEs) associated with pembrolizumab alone or in combination with other drugs in patients with mCRPC.

They conducted a comprehensive search across biomedical databases from 2018 to 2023, including MEDLINE®, EMBASE®, and PubMed. Supplementary searches were also conducted to compile evidence from grey literature sources. 2 researchers independently performed the analysis of the included studies, with 3rd researcher resolving any conflicts.

About 118 studies were identified, with 12 meeting the inclusion criteria. Among them, 8 were phase 1/2 studies (n=08). Anemia (27%), febrile neutropenia (12%), fatigue (5.9%), and decreased neutrophil count (5.8%) were the most common grade 3-5 treatment-related adverse events (TRAEs). Chills (89.2%), pyrexia (54.1%), and nausea (45.9%) were frequently reported TRAEs of any grade or grade 1-2.

In the remaining 4 studies, anemia (19.6%), fatigue (3%), and asthenia (2.3%) were the prominent grade 3-5 TRAEs, while anemia (46%), nausea (35.6%), and fatigue (25.7%) were the most reported TRAEs of any grade. Fatigue (66.7%) and hot flashes (50%) were common grade 1-2 AE’s.

The study concluded that pembrolizumab exhibited a notable occurrence of AEs, predominantly falling within mild to severe grades (grades 1-3), with fatigue being frequently reported. Despite this, the AEs were generally manageable and did not necessitate hospitalization or treatment discontinuation.

The study was sponsored by Merck Sharp & Dohme LLC.


Clinical Trial:

Singla D, Mahapatra S, John A, (2024). “Incidence of Adverse Events with Pembrolizumab in Patients with Metastatic Castration-Resistant Prostate Cancer (mCRPC): A Systematic Review of Literature.” Presented at ISPOR 2024.

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