KEY TAKEAWAYS
- The KEYNOTE-522 phase 3 trial aimed to investigate the OS benefit of adding pembrolizumab to chemotherapy in patients with high-risk early-stage TNBC.
- The primary endpoints were pCR & EFS and the secondary endpoint was OS.
- Researchers observed a significant OS improvement with pembrolizumab plus chemotherapy in high-risk early-stage TNBC.
KEYNOTE-522 (NCT03036488) demonstrated statistically significant and clinically meaningful improvements in pathologic complete response (pCR) and event-free survival (EFS) with the addition of pembrolizumab to chemotherapy in patients with early-stage triple-negative breast cancer (TNBC). The study focused on assessing the long-term impact of this treatment combination.
Peter Schmid and the team aimed to assess the final overall survival (OS) results to further evaluate the benefits of pembrolizumab in this high-risk population.
They performed an inclusive analysis on eligible patients with previously untreated, non-metastatic, centrally confirmed TNBC at stage T1c N1-2 or T2-4 N0-2 according to AJCC criteria. Patients were randomized in a 2:1 ratio to receive either neoadjuvant pembrolizumab (200 mg Q3W) or placebo (pbo).
Both groups were treated with 4 cycles of paclitaxel and carboplatin, followed by 4 cycles of doxorubicin or epirubicin combined with cyclophosphamide. Following definitive surgery, patients received adjuvant pembrolizumab or pbo for up to 9 cycles or until recurrence or unacceptable toxicity occurred.
The study’s dual primary endpoints were (pCR; ypT0/Tis ypN0) and EFS, measured as the time from randomization to disease progression preventing definitive surgery, local or distant recurrence, second primary cancer, or death from any cause. OS was defined as the key secondary endpoint.
About 1174 patients were randomized to the pembrolizumab group (n=784) or the pbo group (n=390). The data cutoff (March 22, 2024), median follow-up duration was 75.1 months (range: 65.9-84.0 months). A total of 115 patients (14.7%) in the pembrolizumab group and 85 patients (21.8%) in the pbo group had died, with a hazard ratio (HR) of 0.66 (95% CI, 0.50-0.87; P=0.0015), meeting the prespecified significance boundary of 0.00503.
The 5-year OS rate (95% CI) was 86.6% (84.0-88.8) in the pembrolizumab group compared to 81.7% (77.5-85.2) in the pbo group. The benefit of pembrolizumab on OS was generally consistent across the prespecified subgroups, including those defined by PD-L1 expression and nodal status.
The 5-year EFS rate (95% CI) was 81.2% (78.3-83.8) for the pembrolizumab group versus 72.2% (67.4-76.4) for the pbo group (HR 0.65 [95% CI, 0.51-0.83]). Grade ≥3 treatment-related adverse event (TRAEs) rates were 77.1% in the pembrolizumab group and 73.3% in the pbo group, with a death incidence of 0.5% versus 0.3%, respectively. Immune-mediated AEs of any grade were reported in 35.0% of the pembrolizumab group compared to 13.1% in the pbo group.
The study concluded that neoadjuvant pembrolizumab combined with chemotherapy, followed by adjuvant pembrolizumab, resulted in a statistically significant and clinically meaningful improvement in OS compared with neoadjuvant chemotherapy alone in patients with high-risk early-stage TNBC.
The trial was sponsored by the Merck Sharp & Dohme LLC.
Source: https://cslide.ctimeetingtech.com/esmo2024/attendee/confcal/show/session/170
Clinical Trial: https://clinicaltrials.gov/study/NCT03036488
Schmid P, Cortés J, Dent R.A, et al. (2024). “Neoadjuvant pembrolizumab or placebo plus chemotherapy followed by adjuvant pembrolizumab or placebo for high-risk early-stage TNBC: Overall survival results from the phase III KEYNOTE-522 study.” Presented at ESMO 2024 (Abstract LBA4).
