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Keytruda in early-stage triple-negative breast cancer led to immune-related adverse effects, including severe GI issues and endocrinopathies.
Early Triple-Negative Breast Cancer
Among patients with early triple-negative breast cancer, treatment with Keytruda (pembrolizumab) demonstrated real-world evidence of immune-related adverse effects (irAEs) comparable with KEYNOTE-522, where endocrinopathies were the most prevalent, though gastrointestinal (GI) irAEs were also prevalent and severe, according to a study in JCO Oncology Practice.
Although Keytruda is increasingly being utilized in early triple-negative breast cancer, the authors of the study emphasize the critical nature of these issues.
According to study authors, “Although our study found similar rates and severity of irAEs compared with the KEYNOTE-522 trial, we found that GI irAEs had higher toxicity grades, Some irAEs may need to be monitored more closely and proactively requiring earlier collaboration with specialists and discussing with patients the risks and benefits of continuing [Keytruda] once they develop an irAE.”
KEYNOTE-522 trial: evaluated the efficacy and safety of Keytruda in combination with chemotherapy for the treatment of high-risk triple-negative breast cancer.
Colitis: inflammation of the colon.
Hypothyroidism: underactive thyroid gland, leading to reduced hormone production.
Clinicopathologic factors: characteristics of a disease that are observed both clinically and pathologically.
During the study, 80 patients developed 100 separate irAEs. In addition, 18 patients experienced more than one multiorgan or multisystem irAEs. The most common irAEs of any severity were gastrointestinal (23%)where colitis and hepatitis were the most common (both 10%), and endocrinopathies (52%), where hypothyroidism was the most common (32%) followed by adrenal insufficiency (15%).
There were 26 irAEs that were severe or worse, which all resulted in hospitalization. The most common severe or worse side effects was 13 cases of gastrointestinal side effects. In addition, 45 patients required systemic steroids, 16 required additional immunosuppressive therapy and 32 patients discontinued Keytruda due to irAEs. Eventually, two patients died due to complications from developing colitis. Although most irAEs were unresolved at the time of the last follow-up, 55% of patients had improved their side effects to a mild impact. The development or severity of irAEs were not associated with clinicopathologic factors.
“We did not find any clinicopathologic characteristics that correlated with development of irAEs, which is an area of research that is greatly needed,” study authors wrote.
A total of 233 patients with a median age of 51 years were included in the trial. Among patients, 62% had stage 2 and 35% had stage 3 triple-negative breast cancer. Patients who were excluded from the trial included those with metastatic disease, incomplete medical documentation, or those who previously participated in therapeutic clinical trials.
Regarding enrollment, this patient population included diverse groups of patients from a country hospital that predominantly attends underserved population. The distribution of race and ethnicity is as follows: 25% of the individuals identified as Hispanic/Latino, 21% as non-Hispanic Black, 6% as Asian and 42% as non-Hispanic White.
“This retrospective study of a real-world diverse patient population with TNBC who received [Keytruda] showed similar rates and severity of irAEs compared with those reported by the KEYNOTE-522 trial. However, the breakdown of the irAEs by organ or system was different, and one unique aspect of our study was having a diverse patient population,” study authors wrote.
The most common histology was invasive ductal carcinoma (94%). Other histologies (4%), included metaplastic carcinoma and invasive carcinoma with neuroendocrine features. Very few cases were invasive lobular carcinoma (1.3%) or invasive mixed ductal/lobular carcinoma (0.4%).
Regarding dosage, patients received four different Keytruda-containing systemic therapy regimens: the KEYNOTE-552 regimen of paclitaxel plus carboplatin followed by doxorubicin and cyclophosphamide (AC; 79%), taxane plus carboplatin (19.3%), AC alone (1.3%) and taxane combined with AC (0.4%).
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Reference
“Real-World Immune-Related Adverse Events in Patients With Early Triple-Negative Breast Cancer Who Received Pembrolizumab” by Dr. Athira Jayan, et al., JCO Oncology Practice.
