KEYTRUDA, an anti-PD-1 therapy, empowers the body's immune system to recognize and combat tumor cells. The FDA's approval of pembrolizumab, in conjunction with chemotherapy, as a neoadjuvant regimen for high-risk, early-stage TNBC, followed by surgery and pembrolizumab monotherapy, is grounded in the pivotal Phase III KEYNOTE-522 study. This landmark trial represents the first prospective Phase III exploration of pembrolizumab's role in both neoadjuvant and adjuvant settings for early-stage TNBC. In contrast to the pre-2021 standard neoadjuvant chemotherapy approach, which relied on dose-dense doxorubicin-cyclophosphamide and paclitaxel, the new gold standard for localized TNBC unites chemotherapy with the power of immunotherapy, marking a significant shift in treatment protocols.

Pembrolizumab, when used in combination with chemotherapy, is considered a Category 1, preferred first-line treatment option for tumors with a PD-L1 CPS (Combined Positive Score) of 10 or higher, regardless of the patient's germline BRCA1/2 mutation status. PD-L1 expression is evaluated using the 22C3 antibody, and a tumor CPS of 10 or higher is the threshold for determining positivity.

As of the March 2023 data cutoff, the median follow-up stood at 63.1 months, revealing an impressive 60-month event-free survival rate of 81.3% for those treated with pembrolizumab, compared to 72.3% for the non-pembrolizumab group, with no median reached in either cohort. Notably, the EFS advantage associated with pembrolizumab was consistently observed across various subgroups, including those defined by PD-L1 expression and nodal status. In a prespecified, non-randomized analysis, patients achieving a pathological complete response saw outstanding 5-year EFS rates of 92.2% with pembrolizumab and 88.2% without, while those without a pCR still benefitted significantly with rates of 62.6% versus 52.3%. Follow-up for OS is ongoing. 

With ongoing follow-up for overall survival, the combination of KEYTRUDA and chemotherapy is expected to assert its dominance in the first-line treatment of triple-negative breast cancer, aiming to capture a substantial market share in the United States in 2022.

KOL insights

“These results provide further support for pembrolizumab plus platinum-containing neoadjuvant chemotherapy followed by adjuvant pembrolizumab after surgery, regardless of the pCR outcome, as a standard-of-care treatment regimen for patients with high-risk, early-stage TNBC” -MD, PhD, professor of cancer medicine.

Conclusion

KEYTRUDA Receives FDA Approval on the Strength of Pioneering KEYNOTE-522 Study. The research showcases remarkable Event-Free Survival gains through pembrolizumab's inclusion in both neoadjuvant and adjuvant therapy for early-stage TNBC patients, irrespective of complete response status. This underlines the role of pembrolizumab in combination with platinum-based neoadjuvant chemotherapy and adjuvant therapy, setting a new standard for high-risk early-stage TNBC treatment. Particularly effective for TNBC tumors with a PD-L1 CPS score of 10 or higher, KEYTRUDA now stands as a cornerstone of first-line therapy, transcending BRCA1/2 mutation status. Ongoing research continues to fortify the position of KEYTRUDA and chemotherapy as the leading choice for TNBC management.

For more insight into the patient's burden/epidemiology, treatment, and changing market landscape-related advancements, refer to Triple Negative Breast Cancer (TNBC) Market Forecast Report