Pembrolizumab Demonstrates Durable EFS and OS Benefit in High-Risk TNBC

At the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting, Peter Schmid, MD, PhD, of the Centre for Experimental Cancer Medicine, Barts Cancer Institute, Queen Mary University London, London, UK, presented final analysis results from the phase 3 KEYNOTE-522 trial (NCT03036488) evaluating perioperative pembrolizumab (Keytruda) plus chemotherapy in patients with high-risk, early-stage triple-negative breast cancer (TNBC).¹

At the final analysis, event-free survival (EFS) events were recorded in 21.9% of pembrolizumab-treated patients (172 of 784) vs 30.3% in the placebo arm (118 of 390), yielding a hazard ratio (HR) of 0.68 (95% CI, 0.54–0.86). The estimated 7-year EFS rate was 78.3% with pembrolizumab compared with 69.8% with placebo. These results extended the significant EFS benefit first established at interim analysis 4 at approximately 39 months of follow-up (HR, 0.63; 95% CI, 0.48–0.82; P = .00031). In prespecified EFS subgroup analyses, the pembrolizumab benefit was generally consistent across nodal status, tumor size, carboplatin schedule, and PD-L1 combined positive score (CPS)— including patients with a CPS of less than 1 (HR, 0.56; 95% CI, 0.34–0.93)—with no differential harm signals identified.

Pembrolizumab also demonstrated a sustained overall survival (OS) benefit at the final analysis, with events in 15.3% (120 of 784) vs 23.1% (90 of 390) of patients in the pembrolizumab and placebo arms, respectively (HR, 0.64; 95% CI, 0.49–0.85). The estimated 7-year OS rate was 85.1% with pembrolizumab vs 77.2% with placebo. The distant progression-free or distant recurrence-free survival rate at 7 years was 82.9% vs 74.2% (HR, 0.64; 95% CI, 0.49–0.83). Importantly, the OS advantage was observed regardless of patholgoical complete response (pCR) status; among patients who achieved pCR, the OS HR was 0.64 (95% CI, 0.37–1.14), and among those who did not, the HR was 0.76 (95% CI, 0.55–1.03).

The double-blind trial enrolled 1174 patients with newly diagnosed TNBC staged T1c N1-2 or T2-4 N0-2, who were randomly assigned 2:1 from March 2017 to September 2018. In the neoadjuvant phase, patients received carboplatin plus paclitaxel followed by doxorubicin or epirubicin plus cyclophosphamide, with pembrolizumab at 200 mg every 3 weeks or placebo overlapping both chemotherapy sequences. After definitive surgery, patients continued pembrolizumab or placebo for 9 adjuvant cycles (27 weeks).

Dual primary end points were pCR (ypT0/Tis ypN0) and EFS; OS was the key secondary end point. The protocol-specified final analysis was conducted at a data cutoff of October 14, 2025, with a median follow-up of 93.8 months (range, 84.7–102.8).

The safety profile was consistent with prior analyses and the known profiles of pembrolizumab and chemotherapy. Treatment-related adverse events (TRAEs) of any grade occurred in 98.9% of the pembrolizumab group vs 99.7% of the placebo group; grade 3 to 5 TRAEs were reported in 77.1% vs 73.3%. TRAEs led to discontinuation of any study drug in 27.6% vs 14.1%, respectively. Immune-mediated AEs occurred in 35.0% vs 13.1%, with grade 3 to 5 events in 13.0% vs 1.5%. The most frequently reported immune-mediated AEs in the pembrolizumab arm included hypothyroidism (15.1%), severe skin reactions (5.7%), hyperthyroidism (5.2%), and gastritis (3.4%). No new safety signals were identified.

The investigators concluded that at approximately 8 years of follow-up, the KEYNOTE-522 final analysis confirmed that perioperative pembrolizumab plus platinum-containing chemotherapy provides substantial and clinically meaningful long-term survival benefits for patients with high-risk, early-stage TNBC. The benefit was consistent across prespecified subgroups and was observed regardless of pCR status, with pembrolizumab also reducing distant recurrence rates, an established predictor of favorable long-term outcomes. These results further support perioperative pembrolizumab as a standard-of-care treatment option for this population, alongside a rapidly expanding TNBC landscape that includes recently approved agents in the metastatic setting and new frontline combination data continuing to emerge.^2,3

References

1. Schmid P, Cortes J, Dent R, et al. Neoadjuvant pembrolizumab or placebo plus chemotherapy followed by adjuvant pembrolizumab or placebo for high-risk early-stage triple-negative breast cancer: final analysis from the phase 3 KEYNOTE-522 study. J Clin Oncol. 2026;44(suppl 16):507. doi:10.1200/JCO.2026.44.16_suppl.507
2. FDA approves datopotamab deruxtecan-dlnk for unresectable or metastatic triple-negative breast cancer. News release. FDA. May 22, 2026. Accessed June 1, 2026. https://tinyurl.com/2s45pcrr
3. Tolaney SM, Schmid P, de Azambuja E, et al. ASCENT-04: Analysis of efficacy by biomarker subgroups with sacituzumab govitecan (SG) + pembrolizumab (pembro) vs chemotherapy (chemo) + pembro in participants (pts) with previously untreated PD-L1+ metastatic triple-negative breast cancer (mTNBC). J Clin Oncol. 2026;44(suppl 16):1013. doi:10.1200/JCO.2026.44.16_suppl.1013