The KEYNOTE-522 regimen is a standard treatment for high-risk, early-stage triple-negative breast cancer (TNBC). This therapeutic strategy integrates systemic chemotherapy and immunotherapy. The approach is sequential, beginning before surgery (neoadjuvant) to shrink the tumor and continuing afterward (adjuvant) to eliminate remaining cancer cells. This regimen has established a new standard of care by demonstrating significant improvements in patient outcomes compared to chemotherapy alone. It requires a defined schedule spanning several months both pre- and post-operation.
The Treatment Protocol Components
The KEYNOTE-522 regimen combines standard chemotherapy agents with the immunotherapy drug Pembrolizumab. Pembrolizumab is a monoclonal antibody that targets the PD-1 protein on immune cells. By blocking this checkpoint, Pembrolizumab helps the immune system recognize and attack the breast cancer cells. This drug is administered intravenously throughout the entire course of treatment.
The chemotherapy backbone consists of four different drugs administered sequentially. The first set includes Carboplatin and Paclitaxel. These are later followed by an anthracycline agent, Doxorubicin or Epirubicin, combined with the alkylating agent Cyclophosphamide. The concurrent immunotherapy potentiates the overall anti-cancer response.
The Neoadjuvant Phase Schedule
The neoadjuvant phase, administered before surgery, is structured into two distinct stages, totaling eight cycles of therapy. The primary goal of this pre-surgical treatment is to achieve a pathologic complete response, meaning no residual invasive cancer is found at the time of operation. Each cycle lasts three weeks, resulting in a total duration of approximately 24 weeks of pre-operative systemic therapy.
The initial four cycles combine Pembrolizumab with Paclitaxel and Carboplatin. Pembrolizumab is administered at a fixed dose of 200 mg intravenously every three weeks. Paclitaxel is typically given weekly for the first three weeks of each cycle. Carboplatin dosing is flexible, administered either weekly or once every three weeks.
Following the completion of the first four cycles, the regimen transitions to the second stage for the remaining four cycles. Chemotherapy switches to Doxorubicin or Epirubicin combined with Cyclophosphamide. Pembrolizumab continues on the same every-three-week schedule. The entire neoadjuvant phase must be completed before the patient proceeds to surgery.
The Adjuvant Phase Schedule
The adjuvant phase begins after the patient has recovered from surgery, aiming to reduce the risk of cancer recurrence. This post-operative phase consists solely of Pembrolizumab monotherapy, dropping all chemotherapy agents. Treatment continues regardless of whether a pathologic complete response was achieved during the neoadjuvant phase.
The schedule involves nine additional cycles of Pembrolizumab, administered every three weeks. This means the adjuvant phase lasts approximately 27 weeks post-surgery. The dose remains consistent at 200 mg per infusion, matching the frequency and dosage used during the neoadjuvant period.
Including the eight cycles given before surgery, the patient receives a total of 17 doses of Pembrolizumab over the entire regimen. The total duration of Pembrolizumab exposure, spanning both phases, typically extends to about one year. The nine cycles of adjuvant Pembrolizumab are a required component of the complete regimen.