Study Reports Real-World Pembrolizumab Toxicity in TNBC

TOPLINE:

In a real-world diverse population of patients with early triple-negative breast cancer (TNBC), 34% of patients who received pembrolizumab developed immune-related adverse events — findings that are comparable, overall, to those from the landmark KEYNOTE-522 trial. However, there were some differences, including higher rates of gastrointestinal (GI) immune-related adverse events, some of which were “severe enough” that pembrolizumab was discontinued.

METHODOLOGY:

• The addition of pembrolizumab to chemotherapy has improved outcomes in patients with TNBC; however, pembrolizumab can induce varied immune-related adverse events, which may lead to severe or lifelong morbidities.
• Researchers evaluated immune-related adverse events in 233 patients (median age, 51 years; 25% Hispanic/Latino; 21% non-Hispanic Black; 42% non-Hispanic White; 6% Asian) with early TNBC who received pembrolizumab with chemotherapy at two centers between 2021 and 2023. Of those included, 62% had stage II and 35% had stage III TNBC.
• A toxicity was considered an immune-related adverse event if it met one of the following: Pathologic confirmation by biopsy, clinical improvement after treatment for the adverse event, or a documented diagnosis by a physician.
• Patients received one of the following pembrolizumab-containing regimens: Paclitaxel plus carboplatin followed by doxorubicin and cyclophosphamide (AC) regimen (79%), taxane plus carboplatin (19.3%), AC regimen (1.3%), or a taxane plus AC (0.4%).
• The median duration of follow-up was 437 days, starting from the time of the first dose of pembrolizumab.

TAKEAWAY:

• Overall, 80 patients (34%) developed a distinct immune-related adverse event (100 distinct events in total), and 18 of these patients (8%) experienced more than one immune-related adverse event. The rate of grade 3 toxicities was 20%, grade 4 was 4%, and grade 5 was 2%; 1% (two patients) died due to complications from pembrolizumab-induced colitis.
• Endocrine toxicities were the most common immune-related adverse event (52%), with hypothyroidism (32%) and adrenal insufficiency (15%) being the most prevalent. GI immune-related adverse events (23%), including colitis (10%) and hepatitis (10%), were more prevalent and severe than those reported in KEYNOTE-522; GI events comprised 50% of all grade 3 or higher events in the current study.
• Overall, 26 immune-related adverse events led to hospitalizations, 45 events required systemic steroids, and 16 required additional immunosuppressive therapy. In addition, 32 patients (14%) discontinued pembrolizumab due to immune-related adverse events.
• A total of 67 immune-related adverse events remained unresolved at the last follow-up, and 55% improved to grade 1. No clinicopathologic factors were associated with the development or severity of immune-related adverse events.

IN PRACTICE:

“Although our study found similar rates and severity of [immune-related adverse events] compared with the KEYNOTE-522 trial, we found that gastrointestinal [immune-related adverse events] had higher toxicity grades,” the authors wrote, emphasizing that some of these adverse events “may need to be monitored more closely and proactively.” Once patients develop an adverse event, it may be important to have a conversation about the risks and benefits of continuing pembrolizumab, the authors noted.

SOURCE:

This study, led by Athira Jayan, MD, The University of Texas MD Anderson Cancer Center in Houston, Texas, was published online in JCO Oncology Practice.

LIMITATIONS:

This study’s retrospective design may have led to underreporting of low-grade immune-related adverse events, such as skin toxicities. Comparing immune-related adverse event rates with those reported in the prospective KEYNOTE-522 trial was challenging due to differences in data collection methods. The sample was restricted to patients treated at MD Anderson Cancer Center or Lyndon B. Johnson Hospital, potentially introducing selection bias. Reliance on clinical documentation from providers to identify immune-related adverse events can also limit accuracy.

DISCLOSURES:

The University of Texas and MD Anderson Cancer Center supported this work. Several authors reported having ties with various sources. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.