September 16, 2024
By Catlin Nalley
Overall survival (OS) results from the Phase III, KEYNOTE-522 study showed a statistically significant and clinically meaningful improvement in OS among patients with high-risk, early-stage triple-negative breast cancer (TNBC) who were treated with neoadjuvant pembrolizumab plus chemotherapy followed by adjuvant pembrolizumab versus those who received neoadjuvant chemotherapy alone (Abstract LBA4).
These findings were recently presented by Peter Schmid, MD, Professor of Cancer Medicine in the Centre for Experimental Cancer Medicine at Barts Cancer Institute, Queen Mary University, London, during ESMO 2024 in Barcelona, and simultaneously published online in the New England Journal of Medicine.
While discussing his team’s research with Oncology Times, Schmid noted, “The overall survival results I’m presenting at ESMO 2024 from the KEYNOTE-522 trial show pembrolizumab plus chemotherapy as neoadjuvant treatment and continued as a single agent after surgery reduced the risk of death by more than one-third compared to neoadjuvant chemotherapy, building on past pathological complete response and event-free survival data from the study.
“Pembrolizumab plus chemotherapy already plays an impactful role in the treatment of patients with high-risk early-stage triple-negative breast cancer, and these new data demonstrate its potential to help patients live longer,” he continued.
KEYTNOTE-522, a prospective, randomized, placebo-controlled, Phase III study, previously met its dual primary endpoints, demonstrating statistically significant and clinically meaningful improvements in pathological complete response and event-free survival with the addition of pembrolizumab to chemotherapy in patients with early-stage TNBC.
Eligible patients with previously untreated, non-metastatic, centrally confirmed TNBC were randomized 2:1 to receive neoadjuvant pembrolizumab (200 mg Q3W) or placebo, both administered with 4 cycles of paclitaxel plus carboplatin, then 4 cycles of doxorubicin or epirubicin plus cyclophosphamide. Following definitive surgery, patients underwent adjuvant pembrolizumab or placebo for 9 cycles or until recurrence or unacceptable toxicity.
“Based on this study, regulatory authorities worldwide have approved pembrolizumab in combination with chemotherapy as a neoadjuvant and adjuvant therapy for patients with Stage 2 or 3 triple-negative breast cancer, and this regimen has been included in standard treatment guidelines,” said Schmid during his ESMO presentation highlighting the analysis’ final overall survival results.
In this analysis, 1,174 patients were randomized to the pembrolizumab (n=784) or placebo (n=390) arms. At the prespecified data cutoff of March 22, 2024, median follow-up was 75.1 months. Reporting on the updated event-free survival data, Schmid noted a 5-year EFS of 81.2 percent for patients treated with chemotherapy and pembrolizumab compared with 72.2 percent for those who received chemotherapy alone.
Data revealed a 5-year overall survival rate of 86.6 percent versus 81.7 percent for the pembrolizumab and placebo groups, respectively. The benefit of pembrolizumab on overall survival was generally consistent across prespecified subgroups, including those defined by PD-L1 expression and nodal status, according to Schmid.
In terms of safety, the Grade ≥3 treatment-related adverse event rates were 77.1 percent among patients who received pembrolizumab and 73.3 percent for those who did not. The investigators observed immune-mediated adverse events for any grade rates of 35.0 percent and 13.1 percent, respectively.
“In summary, neoadjuvant pembrolizumab and chemotherapy followed by adjuvant pembrolizumab resulted in a statistically significant and clinically meaningful improvement in overall survival compared with neoadjuvant chemotherapy alone in patients with previously untreated, Stage II or III triple-negative breast cancer,” Schmid stated. “The overall survival benefit seen in this trial was generally consistent in all prespecified subgroups, including those defined by PD-L1 expression, nodal status, and tumor size, and was observed regardless of pCR outcome.”
According to Schmid, these results offer further support for neoadjuvant pembrolizumab with platinum-containing chemotherapy followed by adjuvant pembrolizumab after surgery as a standard-of-care treatment regimen for patients with high-risk, early-stage TNBC.
Commenting on this research in a statement, Alessandra Curioni-Fontecedro, MD, Professor of Oncology at the University of Fribourg and Director of Oncology at the Hospital of Fribourg, Switzerland, noted, “This study shows improvements with immunotherapy in patients with the most aggressive subtype of breast cancer, where previously we could only offer chemotherapy.
“We had thought that breast cancer may not be sensitive to immunotherapy alone, but giving it in combination with chemotherapy before surgery and then further afterward improves overall survival in many patients,” she continued. “The finding suggests the possibility that the combination of treatments might lead to a sensitization of TNBC to immunotherapy.”
Catlin Nalley is a contributing writer.