Immunotherapy-chemotherapy combination increases response in high-risk breast cancer
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Key takeaways:
- The addition of pembrolizumab to chemotherapy increased pathologic complete response.
- Patients treated with the combination exhibited reduced residual cancer burden.
SAN ANTONIO — An immunotherapy-chemotherapy combination conferred benefit for certain patients with high-risk breast cancer, according to study results presented at San Antonio Breast Cancer Symposium.
The addition of pembrolizumab (Keytruda, Merck) to chemotherapy improved pathologic complete response rate and reduced residual cancer burden among those with early-stage, high-risk ER-positive, HER2-negative disease, Joyce O’Shaughnessy, MD, research co-chair at Baylor University Medical Center and Texas Oncology, reported.
Pembrolizumab is an anti-PD-1 antibody.
The global phase 3 KEYNOTE-756 study included 1,278 patients with early-stage, high-risk ER-positive, HER2-negative breast cancer. All patients had centrally confirmed grade 3 invasive ductal ER-positive, HER2-negative disease.
O’Shaughnessy and colleagues randomly assigned 635 of them to 200 mg neoadjuvant pembrolizumab every 3 weeks plus chemotherapy (paclitaxel weekly for 12 weeks, then four cycles of doxorubicin or epirubicin plus cyclophosphamide), followed by adjuvant pembrolizumab for nine cycles plus standard endocrine therapy. The other 643 received placebo plus neoadjuvant chemotherapy, plus placebo and endocrine therapy in the adjuvant setting.
Investigators stratified by region (Eastern Europe, China or other), tumor PD-L1 status (combined positive score [CPS] 1 or higher vs. CPS < 1), nodal involvement (positive vs. negative), ER positivity ( 10% vs. < 10%) and anthracycline schedule (every 3 weeks vs. every 2 weeks).
Pathologic complete response (defined as ypT0/Tis ypN0) and EFS served as dual primary endpoints. Secondary endpoints included OS, pathologic complete response (defined as ypT0 ypN0 or ypT0/Tis) and safety.
Residual cancer burden assessed at time of surgery served as an exploratory endpoint.
Median follow-up at the final pathologic complete response analysis was 33.2 months (range, 9.7-51.8).
Results showed a significantly higher pathologic complete response rate with pembrolizumab in the intention-to-treat population based on the primary pathologic complete response definition (24.3% vs. 15.6%; estimated difference, 8.5 percentage points; 95% CI, 4.2-12.8). The benefit persisted for secondary pathologic complete response definitions of ypT0 ypN0 (21.3% vs. 12.8%) and ypT0/Tis (29.4% vs. 18.2%).
Pembrolizumab conferred a generally consistent benefit across prespecified patient subgroups.
The addition of immunotherapy also appeared associated with lower residual cancer burden.
Pathologist assessment classified a higher percentage of patients assigned pembrolizumab than placebo as RCB-0 (24.7% vs. 15.6%) or RCB-1 (10.2% vs. 8.1%), denoting less residual cancer burden. A lower percentage of patients assigned pembrolizumab than placebo were classified as RCB-2 (40.8% vs. 45.3%) or RCB-3 (20.5% vs. 28.9%).
The safety profile of each regimen appeared consistent with prior reports.
In the neoadjuvant treatment phase, researchers reported grade 3 or higher treatment-related adverse events among 52.5% of those assigned pembrolizumab-chemotherapy and 46.4% of those assigned placebo-chemotherapy. One patient assigned pembrolizumab died of myocardial infarction.
EFS results remained immature and follow-up for this outcome is ongoing.
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Cardoso F, et a. Abstract GS01-02. Presented at: San Antonio Breast Cancer Symposium; Dec. 5-9, 2023; San Antonio.
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