In the era of chemotherapy alone, patients with high-risk early-stage triple-negative breast cancer (TNBC)—particularly those with node-positive disease or more advanced tumors—continued to face a substantial risk of recurrence after surgery, making cure an ambitious goal for many. Over the past few years, however, immune checkpoint inhibitors (ICIs) and antibody-drug conjugates (ADCs) have rapidly moved from the metastatic setting into early-stage treatment, bringing new hope for long-term survival and potential cure.At the 2026 ASCO Annual Meeting, the final analysis of the landmark KEYNOTE-522 trial demonstrated that the addition of pembrolizumab to perioperative chemotherapy provides durable survival benefits. After seven years of follow-up, both event-free survival (EFS) and overall survival (OS) remained significantly improved. Most strikingly, patients who achieved a pathologic complete response (pCR) after pembrolizumab-based therapy achieved a remarkable 7-year overall survival rate of 94.5%, suggesting that the vast majority of these patients remain alive more than seven years after treatment.
In this edition of ASCO China Perspective, Oncology Frontier invited Professor Kun Wang of Guangdong Provincial People’s Hospital to discuss the clinical significance of these findings, identify the patients most likely to benefit from immunotherapy, and explore future treatment strategies incorporating novel approaches such as ADCs and findings from China’s NeoSACT study.
Expert Commentary
Neoadjuvant Treatment for TNBC: Moving Beyond “Immunotherapy Plus” Toward the ADC Era
Oncology Frontier:
The final analysis of KEYNOTE-522 showed that after a median follow-up of 7.8 years, pembrolizumab continued to deliver clinically meaningful survival benefits, with absolute improvements of 8.5% in 7-year EFS and 7.9% in 7-year OS. What do you consider the most important clinical implication of these long-term findings?
Professor Kun Wang:
KEYNOTE-522 is undoubtedly a landmark study in the field of neoadjuvant treatment for TNBC. When evaluating neoadjuvant therapy, we focus on two major categories of endpoints. The first is the short-term endpoint of pathologic complete response (pCR), while the second—and ultimately the most important—is long-term survival, including event-free survival (EFS), disease-free survival (DFS), and overall survival (OS).
Previous interim analyses of KEYNOTE-522, all published in the New England Journal of Medicine, demonstrated successively that pembrolizumab plus chemotherapy significantly improved pCR, EFS, and eventually OS. Compared with chemotherapy alone, the addition of pembrolizumab increased the pCR rate from 51.2% to 64.8% (P<0.001), improved the 3-year EFS rate from 76.8% to 84.5% (HR 0.63; P<0.001), and increased the 5-year OS rate from 81.7% to 86.6% (P=0.002).
At this year’s ASCO meeting, investigators presented the protocol-specified final analysis after a median follow-up of 93.8 months. The benefits remained durable, with 7-year EFS reaching 78.3% compared with 69.8% in the placebo group (HR 0.68), while the 7-year OS rate increased to 85.1% versus 77.2% (HR 0.64).
It is uncommon for a Phase III perioperative trial in early breast cancer to demonstrate significant improvements in both short-term efficacy, reflected by pCR, and long-term survival, including both EFS and OS. These results provide compelling evidence supporting the clinical value of this treatment strategy.
Based on these findings, neoadjuvant chemotherapy combined with pembrolizumab should now be considered the standard treatment for patients with high-risk early TNBC staged T2N0 or higher.
Oncology Frontier:
KEYNOTE-522 established chemotherapy plus pembrolizumab as the standard neoadjuvant treatment for early TNBC. In routine practice, how do you determine which patients are appropriate candidates for immunotherapy? Besides PD-L1 expression, are there other biomarkers that deserve attention?
Professor Kun Wang:
The population suitable for neoadjuvant chemoimmunotherapy is essentially the same population that historically received neoadjuvant chemotherapy alone—patients with tumors measuring 2 cm or larger (T2 or above) or those with lymph node-positive disease.
One important distinction from metastatic TNBC is that PD-L1 expression is not required in the early-stage setting. Regardless of whether PD-L1 is positive or negative, patients derive statistically significant benefit from the addition of pembrolizumab.
At present, biomarkers should primarily be viewed as tools for identifying patients who may derive greater benefit rather than as criteria for deciding whether treatment should be offered. Even without considering biomarker status, patients with T2 disease or nodal involvement clearly benefit from neoadjuvant chemotherapy combined with immunotherapy.
Therefore, I do not believe we should place excessive emphasis on searching for additional biomarkers simply to determine treatment eligibility. Instead, future research should focus on identifying which patients within this broadly eligible population derive the greatest magnitude of benefit and whether treatment can eventually be further individualized.
Oncology Frontier:
The NeoSACT study that you led achieved a pCR rate of 69%, numerically even higher than the 64.8% reported in KEYNOTE-522, while requiring only 12 weeks of treatment. Could you discuss the rationale behind this study? In addition, several studies are now exploring immunotherapy combined with ADCs in high-risk early TNBC. How do you view these emerging strategies?
Professor Kun Wang:
The NeoSACT study was inspired by advances in the treatment of metastatic TNBC. Clinical studies in advanced disease have demonstrated that anti-angiogenic therapy can act synergistically with immunotherapy. This prompted us to investigate whether the same synergistic effect could be translated into the neoadjuvant treatment of early-stage TNBC.
The results were encouraging. Following neoadjuvant chemotherapy combined with immunotherapy and anti-angiogenic therapy, the study achieved an overall pCR rate of 69%. Particularly noteworthy was the excellent efficacy observed among PD-L1-negative patients, whose pCR rate reached 75%. These findings suggest that this treatment strategy represents a highly promising direction for future investigation.
At the same time, antibody-drug conjugates are rapidly reshaping the treatment landscape. Studies such as ASCENT-03 and ASCENT-04, evaluating sacituzumab govitecan, have shown that ADC-based therapy outperforms conventional chemotherapy—and even chemotherapy combined with immunotherapy—in the first-line treatment of metastatic TNBC, regardless of PD-L1 status.
These advances naturally raise important questions for early-stage disease. Could ADCs alone provide superior efficacy in the neoadjuvant setting? Could combining ADCs with immunotherapy produce even better outcomes? Several clinical trials are currently underway to address these questions, and we look forward to seeing their results.
Study Summary
KEYNOTE-522 Final Survival Analysis Demonstrates Durable Benefits of Perioperative Pembrolizumab
KEYNOTE-522 is a randomized Phase III trial evaluating pembrolizumab combined with chemotherapy in patients with high-risk early-stage TNBC. Previous analyses demonstrated statistically significant improvements in pathologic complete response, event-free survival, and overall survival, leading to worldwide regulatory approvals and incorporation of the regimen into major clinical practice guidelines.
The study enrolled patients with previously untreated, non-metastatic TNBC staged T1cN1–2 or T2–4N0–2, who were randomized in a 2:1 ratio to receive pembrolizumab or placebo in combination with standard neoadjuvant chemotherapy consisting of paclitaxel plus carboplatin followed by doxorubicin (or epirubicin) plus cyclophosphamide. After surgery, patients continued to receive nine cycles of pembrolizumab or placebo. The co-primary endpoints were pCR and EFS, while OS was a key secondary endpoint. The final analysis was conducted after a median follow-up of 93.8 months.
A total of 1,174 patients were randomized, including 784 assigned to pembrolizumab and 390 to placebo. The final analysis demonstrated sustained long-term efficacy. The 7-year EFS rate was 78.3% in the pembrolizumab group compared with 69.8% in the placebo group, corresponding to a 32% reduction in the risk of an event (HR 0.68; 95% CI 0.54–0.86). Benefits were consistently observed across predefined subgroups regardless of residual nodal disease, tumor stage, or PD-L1 status.
Overall survival was likewise significantly improved. The 7-year OS rate reached 85.1% with pembrolizumab compared with 77.2% with placebo, translating into a 36% reduction in the risk of death (HR 0.64; 95% CI 0.49–0.85). Among patients who achieved a pathologic complete response, outcomes were particularly impressive: the 7-year OS rate reached 94.5%, indicating that nearly all patients achieving pCR after pembrolizumab-based therapy remained alive more than seven years later.
The safety profile remained consistent with previous reports. Grade 3 or higher treatment-related adverse events occurred in 77.1% of patients receiving pembrolizumab and 73.3% of those receiving placebo. Immune-mediated adverse events were more frequent in the pembrolizumab arm (35.0% vs 13.1%), but overall the toxicities were considered manageable and consistent with the known safety profile of pembrolizumab.
Professor Kun Wang
Guangdong Provincial People’s Hospital
