Real-world data from a study of patients who received the KEYNOTE-522 regimen demonstrated an improved pathologic complete response (pCR) compared to what was observed in the original study data. The analysis, published in Annals of Surgical Oncology, highlights the effectiveness of neoadjuvant pembrolizumab (Keytruda) with chemotherapy in early-stage triple-negative breast cancer (TNBC).
The study retrospectively analyzed data from 240 patients diagnosed with stage II or III TNBC who underwent neoadjuvant treatment followed by surgery at the Cleveland Clinic between January 2019 and December 2022. Of these, 86 patients received the KEYNOTE-522 regimen, while 154 were in the control group, receiving the same chemotherapy backbone with a placebo.
Improved Pathologic Complete Response
The KEYNOTE-522 regimen, consisting of pembrolizumab combined with chemotherapy (carboplatin, paclitaxel, doxorubicin, epirubicin, and cyclophosphamide), demonstrated a significantly higher pCR rate of 59.3% compared to 33.1% in the control arm (odds ratio [OR], 0.34; 95% CI, 0.20-0.58; P = .0001). This indicates a substantial improvement in treatment response in the real-world setting.
Reduced Need for Axillary Lymph Node Dissection
In addition to improved pCR rates, the KEYNOTE-522 regimen was associated with a significantly lower rate of axillary lymph node dissection (ALND). The ALND rate was 25.6% in the KEYNOTE-522 group compared to 39.6% in the control arm (P = .03), suggesting that the regimen may reduce the extent of surgical intervention needed.
No Significant Difference in Breast Conservation Therapy
The study found no notable difference in breast conservation therapy (BCT) rates between the two groups, with 32.1% in the KEYNOTE-522 group and 33.1% in the control group (P = .47). This suggests that the use of pembrolizumab with chemotherapy does not significantly impact the likelihood of patients undergoing breast conservation surgery.
Expert Commentary
Julie Lang, MD, professor of surgery and director of the Eastern Region of Cleveland Clinic’s Breast Cancer Program and chief of Breast Surgery at Hillcrest Hospital, noted the impact of the KEYNOTE-522 regimen. "[The KEYNOTE-522] regimen causes the cancer cells in the breast to respond in many patients with TNBC. We suddenly have a regimen that’s highly effective, and we had to adjust our approach accordingly," she stated. "We hope that our findings will help other hospitals design appropriate treatment plans for their own patients as they, too, adopt this new regimen."
Study Details
The median age of the overall patient population was 56 years. The majority of patients had T2 tumors (66%) and grade 3 tumors (83%). Approximately 46% of patients had clinically involved lymph nodes at diagnosis. The primary outcome of the study was to determine if the KEYNOTE-522 regimen was associated with higher pCR rates, which would correspond with higher BCT rates. Secondary outcomes included identifying factors associated with pCR, factors influencing surgical procedure types, and the effect of the regimen on efficacy outcomes.
Patients were eligible for BCT if their solitary tumor measured greater than 4 cm on clinical imaging, or if the total measurement of multifocal disease was greater than 4 cm without evidence of multicentric disease or inflammatory breast cancer.
The KEYNOTE-522 regimen involved intravenous (IV) pembrolizumab on day 1 of each 3-week cycle in both the neoadjuvant and adjuvant phases for a total of 17 cycles. Chemotherapy included IV carboplatin on day 1 of cycles 1 to 4, IV paclitaxel on days 1, 8, and 15 of cycles 1 to 4, doxorubicin via IV injection on day 1 of cycles 5 to 8, epirubicin via IV injection on day 1 of cycles 5 to 8, and IV cyclophosphamide on day 1 of cycles 5 to 8.
Additional Findings
At a median follow-up of 2.4 years, there was no difference in survival outcomes. Patients with BRCA1-mutated disease had higher pCR rates regardless of treatment group, with 80.0% in the KEYNOTE-522 group and 75.0% in the control group.
Regarding safety, 34.9% of patients developed immune-related adverse events (irAEs) of grade 2 or higher. Endocrinopathies accounted for 48% of all irAEs in this study, higher than the 20.4% found in the KEYNOTE-522 trial.
