Survival Gains Confirmed: Full KEYNOTE-522 Data Set to Redefine Treatment Standards in Early-Stage TNBC at ASCO 2026

Ahead of the 2026 ASCO Annual Meeting, results from the final analysis of the phase 3 KEYNOTE-522 study (NCT03036488) have been released.¹

At a median follow-up of 93.8 months (range, 84.7-102.8), treatment with neoadjuvant pembrolizumab plus chemotherapy followed by definitive surgery and adjuvant pembrolizumab elicited a 7-year event-free survival rate of 78.3% (95% CI, 75.3%-81.1%) vs 69.8% (95% CI, 65.0%-74.2%) with neoadjuvant placebo plus chemotherapy followed by surgery and adjuvant placebo (HR, 0.68; 95% CI, 0.54-0.86). The 7-year overall survival (OS) rates in these respective arms were 85.1% (95% CI, 82.5%-87.5%) and 77.2% (95% CI, 72.7%-81.1%; HR, 0.64; 95% CI, 0.49-0.85). These EFS and OS benefits with the pembrolizumab-containing regimen were observed regardless of PD-L1 expression, nodal status, and disease stage.

They build on previously reported data indicating that neoadjuvant pembrolizumab (Keytruda) combined with platinum-containing chemotherapy followed by adjuvant pembrolizumab produced a statistically significant improvement in overall survival (OS) vs neoadjuvant chemotherapy alone in patients with previously untreated, high-risk, early-stage triple-negative breast cancer (TNBC).²

“KEYNOTE-522 was the neoadjuvant/adjuvant study that investigated and led to [the FDA approval of] 1 year of pembrolizumab for patients with early stage II to III disease starting in the neoadjuvant setting along with chemotherapy, followed by surgery and continuation of pembrolizumab [as adjuvant therapy],” Kevin Kalinsky, MD, MS, FASCO, had noted in an exclusive conference preview with OncLive^®.³

Kalinsky is a professor and director of the Division of Medical Oncology in the Department of Hematology and Medical Oncology at the Emory University School of Medicine, as well as the Louisa and Rand Glenn Family Chair in Breast Cancer Research and the director of the Glenn Family Breast Center at the Winship Cancer Institute of Emory University in Atlanta, Georgia. “We already know there’s an improvement in survival, and we’ll see with additional follow-up what that looks like.”

How was the KEYNOTE-522 trial designed?

KEYNOTE-522 is a phase 3, double-blind, randomized, placebo-controlled trial conducted at 183 sites across 21 countries.² Eligible patients were at least 18 years of age, had centrally confirmed, newly diagnosed, nonmetastatic TNBC with T1c N1 to 2 or T2 to 4 N0 to 2 disease per the American Joint Committee on Cancer 7th edition staging criteria, an ECOG performance status no higher than 1, and acceptable organ function. Patients were stratified by nodal status, tumor size, and carboplatin dosing frequency.

A total of 1174 patients were randomly assigned 2:1 to receive pembrolizumab (n = 784) or placebo (n = 390). In the neoadjuvant phase, patients received 4 cycles of pembrolizumab at 200 mg or placebo every 3 weeks plus paclitaxel and carboplatin for 12 weeks, followed by 4 cycles of pembrolizumab or placebo plus doxorubicin or epirubicin and cyclophosphamide. After definitive surgery, patients received up to 9 cycles of adjuvant pembrolizumab or placebo every 3 weeks. The co-primary end points of the trial were pathologic complete response (pCR) and event-free survival (EFS). OS served as a key prespecified secondary end point.

Baseline characteristics revealed that patients in the pembrolizumab arm had a median age of 49 years (range, 22-80) vs 48 years (range, 24-79) for the placebo arm. Less patients in each arm had an ECOG performance status of 1 (pembrolizumab, 13.5%; placebo, 12.6%). Most patients in each arm had a PD-L1 combined positive score of 1 or higher (83.7%; 81%), received carboplatin once a week (57.3%; 57.2%), had T1 or T2 size tumors (74%; 74.4%), and positive nodal involvement (51.7%; 51.3%).

What additional data were reported in KEYNOTE-522?

EFS rates for patients who achieved pathological complete responses (pCR) at median follow-up in each arm were 90.4% for the pembrolizumab arm compared with 85.9% for the placebo arm (HR, 0.68; 95% CI, 0.44-1.07). OS rates for the same population of patients were 94.5% and 91.1% (HR, 0.64; 95% CI, 0.39-1.14) in the pembrolizumab and placebo arm, respectively.

EFS rates among patients who did not achieve pCR were 57.6% in the pembrolizumab arm and 49.7% in the placebo arm (HR, 0.78; 95% CI, 0.59-1.03). OS rates in this population of patients in each of the respective arms were 69% vs 59.8% (HR, 0.76; 95% CI, 0.55-1.03). Moreover, distant progression-free survival rates among all patients in the trial were 82.9% for the pembrolizumab arm and 74.2% for the placebo arm.

Regarding safety, treatment-related adverse effects (TRAES) were experienced by nearly all patients in each arm (pembrolizumab, 98.9%; placebo, 99.7%). Grade 3 or higher TRAEs were common among patients (77.1%; 73.3%), whereas TRAEs that led to treatment discontinuation of any drug (27.6%; 14.1%) or death (0.5%; 0.3%) were less common. Common TRAEs that occurred in patients were nausea (63.5%; 63%), alopecia (60.2%; 56.6%), anemia (54.8%; 55.3%), neutropenia (46.9%; 47.6%), and fatigue (42.3%; 38.8%).

Immune-mediated AEs (imAEs) occurring at any-grade (35%; 13.1%) or grade 3 or higher (13%; 1.5%) were less common among patients. imAEs that led to treatment discontinuation of any drug (7.7%; 1%) or death (0.3%; 0%) were also less common. Common imAEs that were experienced by patients were hypothyroidism (15.1%; 5.7%), severe skin reactions (5.7%; 1%), hyperthyroidism (5.2%; 1.8%), and gastritis (3.4%; 2.1%).

What KEYNOTE-522 data have previously been reported?

Data from the interim analysis of the trial, which had a median follow-up of 15.5 months (range, 2.7-25.0), indicated that the pembrolizumab regimen improved pCR vs chemotherapy alone, at 64.8% (95% CI, 59.9%-69.5%) vs 51.2% (95% CI, 44.1%-58.3%), respectively (difference, 13.6%).⁴ At the fourth interim analysis, which had a median follow-up of 39.1 months, patients who were given pembrolizumab experienced a significant improvement in EFS vs those who received neoadjuvant chemotherapy alone (HR, 0.63; 95% CI, 0.48-0.82; P < .001).⁵ The estimated 36-month EFS rates were 84.5% (95% CI, 81.7%-86.9%) and 76.8% (95% CI, 72.2%-80.7%), respectively.

At a median follow-up of 39.0 months, the pembrolizumab regimen led to a 37% reduction in the risk of disease progression that precluded definitive surgery, a local/distant recurrence, a second primary cancer, or death from any cause (HR, 0.63; 95% CI, 0.48-0.82; P = .00031);⁶ it also resulted in a 28% reduction in the risk of death vs chemotherapy alone (HR, 0.72; 95% CI, 0.31-1.02; P = .03214), although the data had not crossed the boundary for statistical significance at that time point. These data supported the FDA’s decision in July 2021 to clear pembrolizumab for use in patients with high-risk, early-stage TNBC in combination with chemotherapy as neoadjuvant treatment and then continued as a single agent as adjuvant therapy following surgery.⁷

At a median follow-up of 75.1 months, the estimated 5-year OS rate was 86.6% (95% CI, 84.0%-88.8%) in the pembrolizumab/chemotherapy group vs 81.7% (95% CI, 77.5%-85.2%) in the placebo/chemotherapy group, representing an absolute difference of 4.9% (P = .002).² A total of 115 patients (14.7%) in the pembrolizumab/chemotherapy group had died at data cutoff vs 85 patients (21.8%) in the placebo/chemotherapy group.

“What we haven’t [had] until now were the long-awaited OS data. This is only a key secondary end point, but it’s of course, from a patient perspective, the most important end point,” Peter Schmid, MD, PhD, FRCP, of Queen Mary University of London, told OncLive in a past interview.

What is the significance of KEYNOTE-522 for the TNBC paradigm?

“The phase 3 KEYNOTE-522 trial regimen has emerged as our standard treatment for higher-risk TNBC. The 5-year OS rate was improved by 4.9%, and there was a 9% improvement in disease-free survival [in the pembrolizumab (Keytruda) arm vs the placebo arm],” Erika Hamilton, MD, FASCO, told OncLive ahead of ASCO 2026.³ Hamilton is the Late Phase chief development officer and director of Breast Cancer Research at Sarah Cannon Research Institute in Nashville, Tennessee. “This last disclosure will tell us how much benefit patients derive from the addition of pembrolizumab to chemotherapy and give us a new current benchmark for cure rates with modern chemoimmunotherapy in advanced triple-negative disease.”

Javier Cortes, MD, PhD, of Madrid Medica Scientia Innovation Research in Barcelona, Spain, will present the full results as part of a highly anticipated oral abstract session on May 30, 2026.

References

1. Schmid P. Neoadjuvant pembrolizumab or placebo plus chemotherapy followed by adjuvant pembrolizumab or placebo for high-risk early-stage TNBC: final analysis results 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. Schmid P, Cortes J, Dent R, et al. Overall survival with pembrolizumab in early-stage triple-negative breast cancer. N Engl J Med. 2024;391(21):1981-1991. doi:10.1056/NEJMoa2409932
3. Wahner A. ASCO 2026 TNBC deep dive: breast cancer experts preview practice-informing studies. OncLive.com. May 7, 2026. Accessed May 21, 2026. https://www.onclive.com/view/asco-2026-tnbc-deep-dive-breast-cancer-experts-preview-practice-informing-studies
4. Schmid P, Cortes J, Pusztai L, et al. Pembrolizumab for early triple-negative breast cancer. N Engl J Med. 2020;382(9):810-821. doi:10.1056/NEJMoa1910549
5. Schmid P, Cortes J, Dent R, et al. Event-free survival with pembrolizumab in early triple-negative breast cancer. N Engl J Med. 2022;386(6):556-567. doi:10.1056/NEJMoa2112651
6. Keytruda (pembrolizumab) plus chemotherapy before surgery and continued as a single agent after surgery showed statistically significant event-free survival (EFS) result versus neoadjuvant chemotherapy alone in high-risk early-stage TNBC. News release. Merck. July 15, 2021. Accessed May 21, 2026. https://www.merck.com/news/keytruda-pembrolizumab-plus-chemotherapy-before-surgery-and-continued-as-a-single-agent-after-surgery-showed-statistically-significant-event-free-survival-efs-result-versus-neoadjuvant-chemo/
7. FDA approves Keytruda (pembrolizumab) for treatment of patients with high-risk early-stage triple-negative breast cancer in combination with chemotherapy as neoadjuvant treatment, then continued as single agent as adjuvant treatment after surgery. News release. Merck. July 27, 2021. Accessed May 21, 2026. https://www.merck.com/news/fda-approves-keytruda-pembrolizumab-for-treatment-of-patients-with-high-risk-early-stage-triple-negative-breast-cancer-in-combination-with-chemotherapy-as-neoadjuvant-treatment-then-continued/