BREAST CANCER: Conflicting results of neoadjuvant immunotherapy for TNBC, (PD-1 inhibitor pembrolizumab vs atezolizumab)
BREAST CANCER Conflicting results of neoadjuvant immunotherapy for TNBC, with the addition of the PD-1 inhibitor pembrolizumab to chemotherapy improving outcomes but the addition of the PD-L1 inhibitor atezolizumab not. San Antonio Breast, abstracts GS3-03 and GS3-04
SABCS 2019: Does Treatment With Pembrolizumab Improve Pathologic Complete Response in Patients With Triple-Negative Breast Cancer and Lymph Node Involvement?
The addition of the checkpoint inhibitor pembrolizumab to neoadjuvant chemotherapy and as adjuvant therapy increased the rates of pathologic complete response in patients with triple-negative breast cancer who had lymph node involvement, according to results from the KEYNOTE-522 trial, which were presented by Schmid et al at the 2019 San Antonio Breast Cancer Symposium (Abstract GS3-03). Results on pathologic complete response rates from this trial were previously presented at the European Society of Medical Oncology Congress 2019.
The latest data presented at the San Antonio Breast Cancer Symposium included subgroup analyses of patients with lymph node involvement. Peter Schmid, MD, PhD Peter Schmid, MD, PhD “Triple-negative breast cancer is an aggressive subtype of breast cancer with a higher recurrence rate within the first 5 years after diagnosis compared to other subtypes,” said Peter Schmid, MD, PhD, Professor of Cancer Medicine at Barts Cancer Institute in London. “It has been known for some time that involvement of lymph nodes is associated with an even higher risk of recurrence in patients with triple-negative breast cancer.” The current standard of care for early-stage triple-negative breast cancer is chemotherapy.
Large analyses have demonstrated that patients who have a pathologic complete response to neoadjuvant chemotherapy also have low rates of recurrence, particularly in patients with more aggressive cancers like triple-negative breast cancer, explained Dr. Schmid. “Currently, the pathologic complete response rate for standard chemotherapy treatment using an anthracycline and taxane combination is about 40%, or about 50% if a platinum-based drug is added to the combination,” he added. “There continues to be a significant need for new regimens that can increase the pathologic complete response rate and increase long-term, event-free survival for patients with triple-negative breast cancer.”
KEYNOTE-522 Methods In this study, researchers examined the effect of adding the pembrolizumab to neoadjuvant chemotherapy and adjuvant therapy in patients with early-stage triple-negative breast cancer. The study enrolled 1,174 patients aged 18 years or older with previously untreated, nonmetastatic, centrally confirmed triple-negative breast cancer. Patients were randomly assigned 2:1 to receive either pembrolizumab plus chemotherapy or placebo plus chemotherapy as neoadjuvant treatment.
After neoadjuvant treatment, patients underwent definitive surgery and received radiation therapy as indicated. Patients received either adjuvant pembrolizumab or placebo until recurrence or unacceptable toxicity. The primary endpoints of the ongoing study are pathologic complete response and event-free survival. Dr. Schmid and colleagues have previously reported that patients in the pembrolizumab-plus-chemotherapy arm had a significantly higher rate of pathologic complete response compared to patients in the chemotherapy alone arm (64.8% vs 51.2%), regardless of programmed cell death ligand 1 expression.
KEY POINTS Among patients whose cancers had spread to the lymph nodes, 64.8% of those in the pembrolizumab plus chemotherapy arm had a pathologic complete response, compared to 44.1% in the chemotherapy-only arm. High rates of pathologic complete response were also observed in patients with stage III disease.
The latest data presented here showed that among patients whose cancers had spread to the lymph nodes, 64.8% of those in the pembrolizumab-plus-chemotherapy arm had a pathologic complete response, compared to 44.1% in the chemotherapy-only arm. High rates of pathologic complete response were also observed in patients with stage III disease. “Our results suggest that adding pembrolizumab to neoadjuvant chemotherapy is beneficial for patients with the most aggressive disease and the highest unmet need,” said Dr. Schmid. “I think the results have the potential to be practice-changing.” A limitation of the study is that event-free analyses are still preliminary, as the study is ongoing. “After 15 months of follow-up, we see a strong favorable trend for event-free survival, but it has not yet met the predefined boundaries of statistical significance. Additional analyses will follow in the near future,” he concluded.
Luca Gianni, MD, on the Neoadjuvant Treatment of Triple-Negative Breast Cancer
Luca Gianni, MD, of the Fondazione Michelangelo, discusses findings from the NeoTRIP trial on pathologic complete response to neoadjuvant treatment with or without atezolizumab in triple-negative, early high-risk, and locally advanced breast cancer (Abstract GS3-04).