Older Patients With Early Breast Cancer May Have Worse Immune Side Effects

Older patients who previously received immune checkpoint inhibitors for early-stage breast cancer may have an increased risk of developing high-grade immune-related side effects, according to findings from a multi-institutional study presented at the 2024 San Antonio Breast Cancer Symposium (SABCS).

Specifically, the occurrence of any- and high-grade immune-related side effects were 72.6% and 18.9%, respectively, in patients with early-stage breast cancer who received immune checkpoint inhibitors. Among the patient population, Dr. Alexis LeVee and colleagues demonstrated the distribution of any- and high-grade immune-related side effects. Regarding any-grade immune-related side effects, none were observed in 27% of patients, one was observed in 43%, two was observed in 23%, three was observed in 5.7%, four was observed in 1.2% and five was observed in 0.2%. Of note, no high-grade immune-related side effects occurred in 81% of patients, one was observed in 17% and two were observed in 1.7%. There were no high-grade immune-related side effects reported after two.

“The rate of [immune-related side effects] may be higher in our study compared [with] that observed in KEYNOTE-522 due to differences in patient populations, with our study consisting of older patients who may have had more comorbidities,” LeVee and colleagues wrote in the poster presentation.

LeVee is chief fellow, Hematology and Medical Oncology at City of Hope in Los Angeles, California.

KEYNOTE-522 was a phase 3 trial that evaluated previously untreated patients with stage 2 or 3 triple-negative breast cancer, a study that was published in The New England Journal of Medicine. Patients on the trial were either treated with neoadjuvant (presurgical) therapy with Keytruda (pembrolizumab) plus paclitaxel and carboplatin (chemotherapy) or placebo (inactive drug) plus paclitaxel and carboplatin. The incidence of treatment-related side effects of grade 3 (severe) or greater was 78.0% in the Keytruda group versus 73.0% in the placebo group.

The multi-institutional study included patients with stages 1 to 3 breast cancer who received immune checkpoint inhibitors at four academic institutions between 2014 and 2024.

Regarding patient demographics, any-grade immune-related side effects occurred in 307 patients and did not occur in 116. Median age was 51.0 and 50.5 in patients from the any-grade immune-related side effects cohort who did and did not have any-grade immune-related side effects, respectively. Regarding menopausal status, 155 patients (50.5%) and 61 patients (52.6%) were premenopausal among those who experienced any-grade immune-related side effects and those who did not, respectively. Postmenopausal status was reported in 148 (48.2%) and 52 (44.8%) patients, and unknown menopausal status was reported in 4 (1.3%) and 3 (2.6%) patients. Body mass index (BMI) was 27.0 and 27.3. Among patients who did and did not experience any-grade immune-related side effects, respectively, 199 (64.8%) and 56 (48.3%) of patients were White, 25 (8.1%) and 27 (23.3%) were Hispanic, 26 (8.5%) and 10 (8.6%) were Black, 30 (9.8%) and 12 (10.3%) were Asian or Pacific Islander, 1 (0.3%) and 2 (1.7%) were American Indian, and 26 (8.5%) and 9 (7.8%) were unknown.

Smoking status and comorbidities were also observed among patients in the study. In patients from the any-grade immune-related side effects cohort who did and did not experience any-grade immune-related side effects, respectively, 12 (3.9%) and 4 (3.4%) patients were current smokers, 101 (32.9%) and 32 (27.6%) were former smokers, 193 (62.9%) and 80 (69.0%) were never smokers, and 26 (8.5%) and 9 (7.8%) were unknown. Autoimmune disease was reported in 30 (9.8%) and 5 (4.3%), diabetes mellitus in 35 (11.4%) and 12 (10.3%), hypertension in 85 (27.7%) and 34 (29.3%), hyperlipidemia in 51 (16.6%) and 15 (12.9%), CKD in 12 (3.9%) and 1 (0.9%), preexisting lung disease 102 (33.2%) and 35 (30.2%), and coronary artery disease in 12 (3.9%) and 2 (1.7%).

Patient demographics for the high-grade immune-related side effects cohort included 80 patients who experienced high-grade immune-related side effects and 343 who did not experience high-grade immune-related side effects. Median age was 53.5 and 50.0 in patients from the high-grade immune-related side effects cohort who did and did not experience high-grade immune-related side effects, respectively. Regarding menopausal status, 34 patients (42.5%) and 182 patients (53.1%) were premenopausal among those who experienced high-grade immune-related side effects and those who did not, respectively. Postmenopausal status was reported in 45 (56.2%) and 155 (45.2%) patients, and unknown menopausal status was reported in 1 (1.3%) and 6 (1.7%) patients. BMI was 26.1 and 27.4. Among patients who did and did not experience high-grade immune-related side effects, respectively, 54 (67.5%) and 201 (58.6%) of patients were White, 5 (6.3%) and 47 (13.7%) were Hispanic, 3 (3.8%) and 33 (9.6%) were Black, 11 (13.8%) and 31 (9.0%) were Asian or Pacific Islander, 1 (1.3%) and 2 (0.6%) were American Indian, and 6 (7.5%) and 29 (8.5%) were unknown.

Smoking status and comorbidities were also observed among patients in the study. In patients from the high-grade immune-related side effects cohort who did and did not experience high-grade immune-related side effects, respectively, 3 (3.8%) and 13 (3.8%) patients were current smokers, 18 (22.5%) and 115 (33.5%) were former smokers, 58 (72.5%) and 215 (62.7%) were never smokers, and 1 (1.3%) and 0 (0%) were unknown. Autoimmune disease was reported in 8 (10.0%) and 27 (7.9%), diabetes mellitus in 12 (15.0%) and 35 (10.2%), hypertension in 22 (27.7%) and 97 (28.3%), hyperlipidemia in 10 (12.5%) and 56 (16.3%), CKD in 7 (8.8%) and 6 (1.7%), preexisting lung disease 32 (40.0%) and 105 (30.6%) and coronary artery disease in 5 (6.3%) and 9 (2.6%).

Immune-Related Side Effects Experienced By Patients

“Univariate analysis showed that patients [who are White] … were at higher risk of any-grade [immune-related side effects], while older patients, never smokers, and those with chronic kidney disease were at higher risk of high-grade [immune-related side effects],” LeVee and colleagues wrote on the poster.

The most common types of any-grade immune-related side effects included thyroiditis (inflamed thyroid gland; 112 patients), rash (106 patients), colitis (inflamed large intestine; 67 patients), hepatitis (inflamed liver; 49 patients), adrenal insufficiency/hypophysitis (inflamed pituitary glad; 35 patients), arthralgia (joint pain; 25 patients), pneumonitis (inflamed lungs; 11 patients) and diabetes mellitus (eight patients). The majority of these immune-related side effects were grades 1 or 2 (mild or serious).

“Further research is necessary to identify risk factors and biomarkers of immune-related side effectin patients with early breast cancer to help prevent immune-related side effectand mitigate long-term complications,” LeVee and colleagues concluded.

References:

“Incidence and Risk Factors of Immune-Related Adverse Events in Early-Stage Breast Cancer Patients: Findings from a Multi-Institutional Study” by Dr. Alexis LeVee, et al. Presented at: 2024 San Antonio Breast Cancer Symposium; December 10-13, 2024; San Antonio, TX. Abstract PS5-03.

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