KEYNOTE-522
Pembrolizumab plus chemotherapy versus placebo plus chemotherapy as neoadjuvant therapy, then pembrolizumab versus placebo as adjuvant therapy, in early triple-negative breast cancer
Phase 3N = 1,174NCT03036488
- Population
- Previously untreated stage II or stage III triple-negative breast cancer
- Design
- Randomised 2:1, placebo-controlled phase 3 trial. Neoadjuvant pembrolizumab or placebo every 3 weeks with paclitaxel and carboplatin for four cycles, then with doxorubicin-cyclophosphamide or epirubicin-cyclophosphamide for four cycles; after definitive surgery, pembrolizumab or placebo every 3 weeks for up to nine cycles. Registry record: double-blind.
- Primary endpoint
- pCR, EFS
- Arms
- Pembrolizumab plus chemotherapy (experimental, n = 784): Neoadjuvant pembrolizumab 200 mg plus paclitaxel-carboplatin, then pembrolizumab plus anthracycline-cyclophosphamide; adjuvant pembrolizumab
- Placebo plus chemotherapy (control, n = 390): Neoadjuvant placebo plus paclitaxel-carboplatin, then placebo plus anthracycline-cyclophosphamide; adjuvant placebo
- People
- Schmid P, KEYNOTE-522 Investigators
Δ pCR+13.6 pointsEFSHR 0.63 (95% CI 0.48–0.82)Δ 36-month EFS+7.7 pointsΔ 60-month OS+4.9 points
Show the numbers
| Endpoint | Analysis | Pembrolizumab plus chemotherapy | Placebo plus chemotherapy | Effect |
|---|---|---|---|---|
| pCRFirst 602 randomised patients (first interim analysis)No invasive cancer in the breast and negative nodes at definitive surgery | interimSchmid 2020 | 64.8% (59.9–69.5%) | 51.2% (44.1–58.3%) | P<0.001First 602 randomised patients. Estimated treatment difference 13.6 percentage points (95% CI 5.4 to 21.8). Across all treatment phases, grade 3 or higher treatment-related adverse events occurred in 78.0% (pembrolizumab-chemotherapy) and 73.0% (placebo-chemotherapy), including death in 0.4% (3 patients) and 0.3% (1 patient). |
| EFSTime from randomisation to disease progression precluding definitive surgery, local or distant recurrence, second primary cancer, or death from any cause | interimmedian follow-up 39.1 monthsSchmid 2022 | 84.5% at 3 y (81.7–86.9%) | 76.8% at 3 y (72.2–80.7%) | HR 0.63 (95% CI 0.48–0.82)P<0.001Primary endpoint; reported at the fourth planned interim analysis. |
| OS | finalmedian follow-up 75.1 monthsSchmid 2024 | 86.6% at 5 y (84.0–88.8%) | 81.7% at 5 y (77.5–85.2%) | P=0.002Overall survival was a secondary endpoint. The abstract gives no hazard ratio. |
| Endpoint | Analysis | Pembrolizumab plus chemotherapy | Placebo plus chemotherapy | Effect |
|---|---|---|---|---|
| pCRFirst 602 randomised patients (first interim analysis)No invasive cancer in the breast and negative nodes at definitive surgery | interimSchmid 2020 | 64.8% (59.9–69.5%) | 51.2% (44.1–58.3%) | P<0.001First 602 randomised patients. Estimated treatment difference 13.6 percentage points (95% CI 5.4 to 21.8). Across all treatment phases, grade 3 or higher treatment-related adverse events occurred in 78.0% (pembrolizumab-chemotherapy) and 73.0% (placebo-chemotherapy), including death in 0.4% (3 patients) and 0.3% (1 patient). |
| EFSTime from randomisation to disease progression precluding definitive surgery, local or distant recurrence, second primary cancer, or death from any cause | interimmedian follow-up 39.1 monthsSchmid 2022 | 84.5% at 3 y (81.7–86.9%) | 76.8% at 3 y (72.2–80.7%) | HR 0.63 (95% CI 0.48–0.82)P<0.001Primary endpoint; reported at the fourth planned interim analysis. |
| OS | finalmedian follow-up 75.1 monthsSchmid 2024 | 86.6% at 5 y (84.0–88.8%) | 81.7% at 5 y (77.5–85.2%) | P=0.002Overall survival was a secondary endpoint. The abstract gives no hazard ratio. |
Data table
| Endpoint | HR | 95% CI |
|---|---|---|
| EFS | 0.63 | 0.48–0.82 |
Appears in
Sources
Schmid P, Cortes J, Pusztai L, McArthur H, Kümmel S, Bergh J, et al. Pembrolizumab for Early Triple-Negative Breast Cancer. N Engl J Med. 2020;382(9):810-821.
Schmid P, Cortes J, Dent R, Pusztai L, McArthur H, Kümmel S, et al. Event-free Survival with Pembrolizumab in Early Triple-Negative Breast Cancer. N Engl J Med. 2022;386(6):556-567.
Schmid P, Cortes J, Dent R, McArthur H, Pusztai L, Kümmel S, et al. Overall Survival with Pembrolizumab in Early-Stage Triple-Negative Breast Cancer. N Engl J Med. 2024;391(21):1981-1991.