Pembrolizumab improves breast cancer treatment regardless of age or menopausal status

Pembrolizumab improves breast cancer treatment regardless of age or menopausal status

New data from the Phase 3 clinical trial KEYNOTE-756 shows that adding the immunotherapy drug pembrolizumab to chemotherapy before and after breast cancer surgery results in better outcomes for patients, regardless of their age or menopausal status.

The results, presented today (Wednesday) at the 14th European Breast Cancer Conference (EBCC 14), add to the available information on the effects of pembrolizumab in patients with early-stage breast cancer that is at high risk of recurrence or further spread and is estrogen receptor positive (ER positive) and HER2 negative.

KEYNOTE-756 is an international trial that has been running for eight years. 1,278 patients were randomized to receive pembrolizumab or placebo in addition to neoadjuvant chemotherapy (administered before surgery), followed by adjuvant (administered after surgery) pembrolizumab or placebo in combination with endocrine therapy. The patients had invasive ductal carcinoma (IDC), meaning the cancer had begun to spread from the milk ducts into the surrounding breast tissue.

Professor Javier Cortés, director of the International Breast Cancer Center in Barcelona, ​​Spain, said: "We have previously reported that there was a statistically significant increase in the pathological complete response rate in patients who received pembrolizumab compared to those who received placebo." The response rate, meaning no cancer cells remained in the breast or lymph nodes, was 24.3% in patients treated with pembrolizumab, compared with 15.6% in patients treated with placebo.

"Now we can show that these pCR rates occurred regardless of the age or menopausal status of the patients. In patients younger than 50 years, the pCR rate was 23.8% in those receiving pembrolizumab (76 of 319 patients) compared to 16.9% (55 of 326) in those receiving placebo, and was 24.7% (78 of 316 patients) versus 14.2 % (45 of 317). In women aged 50 years or older, the pCR rate was 23.4% (83 of 354) versus 16.1% (57 of 353), and in postmenopausal women it was 24.8% (69 of 278 patients) and 14.6% (42 of 287), respectively.

"We also found that the addition of pembrolizumab to neoadjuvant chemotherapy did not delay time to surgery. The average time to surgery was approximately one month in both groups of patients. The average time after surgery to start of adjuvant treatment was 1.2 months in both groups." .”

The study found that similar rates of breast-conserving surgery and mastectomy occurred in both groups. Of the patients who underwent breast-conserving surgery, 41.3% (262 patients) received pembrolizumab and 43.7% (281 patients) received placebo. Of those who underwent mastectomy, 55.3% (351 patients) were treated with pembrolizumab and 54.4% (350 patients) received placebo.”

Tissue removed at the time of surgery was analyzed to determine whether cancer cells were still present after neoadjuvant treatment, called residual cancer load (RCB). Neoadjuvant pembrolizumab resulted in lower RCB in more patients, regardless of how well the immunotherapy blocked a protein called PD-L1, which also causes some breast cancers.

Pathology reports revealed that 35% of patients treated with pembrolizumab (222 patients) had no or very small amounts of cancer cells remaining (RCB 0-1), compared to 23.6% of patients (152) who received placebo. A moderate amount of RCB (RCB-2) was found in 40.8% of pembrolizumab-treated patients versus 45.3% (259 versus 291 patients), and extensive RCB (RCB-3) was found in 20.5% versus 28.9% of patients (130 versus 186 patients).

When researchers examined the effect of pembrolizumab according to whether patients had cancer that was ER-positive in fewer than 10% of cells or in 10% or more, they found that 64.7% of patients (22 of 34) had fewer than 10 ER-positive cells patients (16 of 43). Among patients with 10% or more ER-positive cells, 33.3% versus 22.7% had RCB-0-1 status (200 of 601 patients versus 136 of 600 patients).

Dr. Fatima Cardoso, director of the breast department at the Champalimaud Clinical Center, Lisbon, Portugal, is the study's principal investigator. Speaking at EBCC 14, she said: "The Keynote 756 trial showed that the addition of pembrolizumab to neoadjuvant chemotherapy significantly increased the pathological response at the time of surgery, and this was independent of PD-L1 levels and estrogen receptor positivity. However, we have seen." greater benefit in higher PD-L1 levels and in ER-low tumors.

“Keynote-756 is also the only study designed to analyze the impact of immunotherapy on long-term outcomes for this subtype of breast cancer.”

The side effects of the treatments remained unchanged from previous reports from the study and were consistent with what is already known about each therapy.

The study continues to follow patients and collect information about survival rates and whether there are recurrences of cancer or other associated symptoms.

Professor Michail Ignatiadis of the Jules Bordet Institute in Brussels, Belgium, is chair of the 14th European Breast Cancer Conference and was not involved in the research.

We have heard additional data from the KEYNOTE-756 trial on 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 pCR rates results in more patients living longer without their disease recurrence, and we look forward to these data in due course.”

Professor Michail Ignatiadis, Jules Bordet Institute in Brussels, Belgium

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