The addition of the immunotherapy drug pembrolizumab to chemotherapy prior to and following surgery may lead to improved outcomes in patients with breast cancer regardless of their age or menopausal status, according to new findings presented by Cardoso et al at the 2024 European Breast Cancer Conference (EBCC) (Abstract 4). The research adds to data on the effect of pembrolizumab on early-stage, estrogen receptor (ER)-positive, HER2-negative breast cancer at high risk of recurrence or metastasis.
Study Methods and Results
In the international phase III KEYNOTE-756 trial, researchers randomly assigned 1,278 patients with invasive ductal carcinoma to receive pembrolizumab or placebo in addition to neoadjuvant chemotherapy followed by adjuvant pembrolizumab or placebo in combination with an endocrine therapy.
“We have already reported that there was a statistically significant increase in the pathologic complete response rate in patients receiving pembrolizumab compared [with] those receiving … placebo. The pathologic complete response rate … was 24.3% in patients treated with pembrolizumab compared [with] 15.6% in patients treated with … placebo,” revealed co–study author Javier Cortés, MD, PhD, Director of the International Breast Cancer Centre in Barcelona.
Dr. Cortés and his colleagues also discovered that among patients under 50 years, the pathologic complete response rate was 23.8% (n = 76/319) in the pembrolizumab group compared with 16.9% (n = 55/326) in the placebo group; among those aged 50 years or older, the pathologic complete response rate was 24.7% (n = 78/316) in the pembrolizumab group vs 14.2% (n = 45/317) in the placebo group. Among premenopausal women, the pathologic complete response rate was 23.4% (n = 83/354) vs 16.1% (n = 57/353), respectively, and among postmenopausal women, the pathologic complete response rate was 24.8% (n = 69/278 patients) vs 14.6% (n = 42/287), respectively.
“Now we can show that these [pathologic complete response] rates occurred regardless of the patients’ age or menopausal status. We also found that adding pembrolizumab to neoadjuvant chemotherapy did not delay the time to surgery. The average time to surgery in both groups of patients was about 1 month. The average time after surgery to the start of adjuvant treatment was 1.2 months in both groups,” Dr. Cortés added.
The researchers found there were similar rates of breast-conserving surgery and mastectomy in both groups. Among the patients who underwent breast-conserving surgery, 41.3% (n = 262) of them received pembrolizumab and 43.7% (n = 281) received placebo; whereas 55.3% (n = 351) of the patients who received pembrolizumab and 54.4% (n = 350) of those who received placebo underwent mastectomy.
After analyzing tissue samples collected at the time of surgery for residual cancer burden following neoadjuvant treatment, they determined that the patients who received neoadjuvant pembrolizumab experienced lower residual cancer burden irrespective of how well the drug blocked PD-L1. The pathology reports demonstrated that 35.0% (n = 222) of the patients who received pembrolizumab vs 23.6% (n = 152) of those who received placebo had no or very small amounts of residual cancer burden. Further, 40.8% (n = 259) and 20.5% (n = 130) of the patients in the pembrolizumab group vs 45.3% (n = 291) and 28.9% (n = 186) of those in the placebo group experienced a moderate and extensive amount of residual cancer burden, respectively.
Additionally, among the patients with ER-positive breast cancer in less than 10% of their cancer cells, 64.7% (n = 22/34) of those in the pembrolizumab group and 37.2% (n = 16/43) of those in the placebo group had no or very small amounts of residual cancer burden. Conversely, among the patients with ER-positive breast cancer in 10% or more of their cancer cells, a respective 33.3% (n = 200/601) vs 22.7% (n = 136/600) of the patients had no or very small amounts of residual cancer burden.
The researchers reported that adverse events from the treatments were unchanged compared to previous reports from the KEYNOTE-756 trial and were consistent with what is already understood about each regimen.
Conclusions
“[The] KEYNOTE-756 trial showed that the addition of pembrolizumab to neoadjuvant chemotherapy significantly increased pathologic [complete] response at the time of surgery, and this was true regardless of PD-L1 levels and [ER] positivity. However, we saw a bigger benefit with higher PD-L1 levels and in ER-low tumors,” emphasized lead study author Fatima Cardoso, MD, FESMO, Director of the Breast Unit at the Champalimaud Clinical Centre in Lisbon. “KEYNOTE-756 is also the only trial that is powered to analyze the impact of immunotherapy in long-term outcomes for this subtype of breast cancer,” she continued.
The researchers plan to continue following the patients to collect data on survival and cancer recurrence rates.
“We have heard more data from the KEYNOTE-756 trial about which ER-positive, HER2-negative patient subgroups benefit most from pembrolizumab in terms of pathologic complete response. Longer follow-up is needed … to see whether the improvement in [pathologic complete response] rates will result in more patients living for longer without their disease recurring, and we look forward to these data in due course,” concluded Michail Ignatiadis, MD, PhD, of the Institut Jules Bordet in Brussels and Chair of the 2024 EBCC, who was not involved in the research.
