Pembrolizumab regimen extends OS in triple-negative breast cancer
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Use of pembrolizumab with neoadjuvant chemotherapy and as monotherapy in the adjuvant setting extended OS for patients with early-stage triple-negative breast cancer, according to results from the randomized phase 3 KEYNOTE-522 trial.
The OS benefit appeared generally consistent across subgroups, including those based on PD-L1 status and nodal expression, findings presented at ESMO Congress showed.
“The overall survival results ... show pembrolizumab plus chemotherapy as neoadjuvant treatment and continued as a single agent after surgery reduced the risk of death by more than one-third compared [with neoadjuvant chemotherapy, building on past pathological complete response and event-free survival data from the study,” Peter Schmid, MD, PhD, clinical director of St. Bartholomew Breast Cancer Centre in London and lead of the Centre for Experimental Cancer Medicine at Barts Cancer Institute, told Healio.
“Pembrolizumab plus chemotherapy already plays an impactful role in the treatment of patients with high-risk early-stage triple-negative breast cancer, and these new data demonstrate its potential to help patients live longer,” Schmid added.
Triple-negative disease is the most aggressive breast cancer subtype. It accounts for 15% to 20% of breast cancer cases and disproportionately affects young women.
KEYNOTE-522 — the first phase 3 trial to evaluate immunotherapy for early breast cancer — assessed the addition of the anti-PD-1 monoclonal antibody pembrolizumab (Keytruda, Merck) to neoadjuvant chemotherapy, followed by adjuvant pembrolizumab.
The trial included 1,174 adults with previously untreated, nonmetastatic, centrally confirmed triple-negative breast cancer.
All patients had stage T1c N1-2 or T2-4 N0-2 disease.
Researchers assigned 784 patients to 200 mg pembrolizumab every 3 weeks in combination with neoadjuvant chemotherapy (four cycles of paclitaxel and carboplatin, followed by four cycles of doxorubicin or epirubicin plus cyclophosphamide). The other 390 patients received chemotherapy plus placebo.
All patients underwent definitive surgery and received radiation therapy as indicated.
Depending on randomization, study participants received adjuvant pembrolizumab or placebo. Adjuvant treatment continued for up to nine cycles, or until disease recurrence or unacceptable toxicity.
Pathologic complete response — defined as ypT0/Tis ypN0, meaning clearance of the cancer from the breast after chemotherapy — and EFS served as dual primary endpoints. Secondary endpoints included OS, efficacy in the subset of patients with PD-L1-positive disease, and safety.
Previously reported results showed statistically significant improvements in pathologic complete response and EFS with pembrolizumab.
The most recent EFS update — based on median follow-up of 63.1 months — showed 145 patients (18.5%) assigned pembrolizumab and 108 patients (27.7%) assigned placebo experienced an EFS event (HR = 0.63; 95% CI, 0.49-0.81).
Results showed 5-year EFS rates of 81.2% with pembrolizumab and 72.2% with placebo (HR = 0.65; 95% CI, 0.51-0.83).
At ESMO, Schmid presented OS data based on median follow-up of 75.1 months (range, 65.9-84). By this time, 115 patients (14.7%) assigned pembrolizumab and 85 patients (21.8%) assigned placebo had died (HR = 0.66; 95% CI, 0.5-0.87).
A higher percentage of patients in the pembrolizumab group remained alive at 5 years (86.6% vs. 81.7%).
A comparable percentage of patients in the pembrolizumab and placebo groups experienced grade 3 or higher treatment-related adverse events (77.1% vs. 73.3%; events leading to death, 0.5% vs. 0.3%).
A higher percentage of patients assigned pembrolizumab developed immune-mediated adverse events of any grade (35% vs. 13.1%).
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Schmid P, et al. Abstract LBA4. Presented at: European Society for Medical Oncology Congress; Sept. 13-17; Barcelona, Spain.
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