Updated results from the phase 3 KEYNOTE-522 trial reveal that neoadjuvant pembrolizumab combined with chemotherapy, followed by adjuvant pembrolizumab, significantly improves overall survival (OS) compared to neoadjuvant chemotherapy plus placebo followed by adjuvant placebo in patients with early-stage triple-negative breast cancer (TNBC). This randomized, double-blind study, which included patients aged 18 years and older with stage II/III TNBC, marks a significant advancement in the treatment of this aggressive cancer.
KEYNOTE-522 Trial Findings
The KEYNOTE-522 trial builds upon earlier findings that showed improved pathologic complete response (pCR) rates with the addition of immunotherapy to chemotherapy in the neoadjuvant setting for TNBC. The latest data, with a median follow-up of 75 months, confirm that these improved responses translate into a substantial long-term survival benefit. At 5 years, event-free survival (EFS) rates were 81% with the pembrolizumab combination compared to 72% with chemotherapy alone. The hazard ratio for EFS remained stable at 0.65, reflecting a 35% reduction in recurrences.
Overall Survival Benefit
Peter Schmid, MD, PhD, of Barts Cancer Institute at Queen Mary University in London, United Kingdom, presented the overall survival data at the ESMO Congress 2024. The results indicated that pembrolizumab added to preoperative chemotherapy significantly improves OS, reducing the risk of death by 34% (HR, 0.66). This benefit was observed across all subgroups, irrespective of PD-L1 status, tumor size, nodal status, or disease stage, making pembrolizumab a viable option for all patients with stage II/III TNBC.
Impact on Pathologic Complete Response
An interesting preplanned analysis examined outcomes based on response to therapy. Patients achieving a pCR with pembrolizumab added to chemotherapy had a 4% lower recurrence risk compared to those receiving chemotherapy alone, suggesting a better quality pCR with the combination. For patients with residual disease, pembrolizumab still provided a substantial benefit, with a 10% improvement in EFS and a 6% improvement in OS compared with chemotherapy alone, indicating that pembrolizumab alters cancer biology, impacting outcomes beyond response to therapy.
Safety Profile
The safety profile of the pembrolizumab combination remains consistent with previous analyses, with no new long-term safety concerns emerging after 6 years of follow-up. The most common adverse effects are primarily chemotherapy-related, with the addition of well-known immune-related adverse effects typical of such agents.
Clinical Implications
According to Dr. Schmid, the KEYNOTE-522 trial has already changed clinical practice and is improving patients' lives. The incorporation of pembrolizumab, along with platinum-based chemotherapy, has led to a reduction in metastatic triple-negative breast cancer rates. The study demonstrates that patients respond better, recurrences are reduced, and the risk of death associated with triple-negative breast cancer is significantly decreased. "This is, for me, practice-changing, and therefore, really important for all clinicians out there," Dr. Schmid stated.
