Event-Free Survival by Residual Cancer Burden After Neoadjuvant Chemotherapy + Pembrolizumab for Early TNBC: KEYNOTE-522 Data

In the KEYNOTE-522 (NCT03036488) study, patients with early-stage triple-negative breast cancer (TNBC) were given pembrolizumab in addition to chemotherapy. The primary end points were pathologic complete response (pCR) and event-free survival (EFS), and the investigators found that pembrolizumab improved pCR and EFS in statistically significant and clinically important ways. The residual cancer burden (RCB) approach for quantifying the degree of remaining disease following neoadjuvant chemotherapy has been demonstrated to have prognostic significance in previous research. In this exploratory investigation, EFS using RCB was evaluated.

Treatment regimens included pembrolizumab 200 mg once every 3 weeks or placebo given with 4 cycles of paclitaxel plus carboplatin, then 4 cycles of doxorubicin or epirubicin plus cyclophosphamide. The study enrolled 1174 patients with previously untreated, nonmetastatic, stage T1c/N1-2 or T2-4/N0-2 TNBC. Patients were given pembrolizumab or placebo for 9 cycles after definitive surgery or until recurrence or intolerable toxicity. RCB was evaluated by a local pathologist at the time of the operation. A Cox regression model with therapy as a covariate was used to investigate the relationship between RCB categories (RCB-0, -1, -2, -3, corresponding to gradually increasing RCB) and EFS.

At the time of data cutoff, the median follow-up was 39.1 months. RCB was relegated to lower categories across the board by pembrolizumab. Hazard ratios for EFS were 0.70 (0.38-1.31) for RCB-0 (equal to pCR), 0.92 (0.39-2.20) for RCB-1, 0.52 (0.32-0.82) for RCB-2, and 1.24 (0.69-2.23) for RCB-3. Distant recurrence was the most prevalent EFS event in both arms; however, it occurred in fewer patients in the pembrolizumab arm in all RCB categories.

Of note, a higher RCB score was linked to a lower EFS. In the pembrolizumab arm, patients with remaining disease had lower RCB levels, including fewer patients with RCB-3. In the RCB-0, -1, and -2 categories, pembrolizumab plus chemotherapy increased EFS compared with chemotherapy alone; however, the small sample size restricts interpretation in the RCB-3 category. A small subset of patients with severe RCB, RCB-3, had a poor prognosis in both arms: 5.1% in the pembrolizumab plus chemotherapy group and 6.7% in the chemotherapy-alone group. These findings underline the relevance of neoadjuvant pembrolizumab therapy for improving survival in patients with early-stage TNBC, representing a subset of patients who may require further therapies.


Pusztai L, Denkert C, O’Shaughnessy J, et al. Event-free survival by residual cancer burden after neoadjuvant pembrolizumab + chemotherapy versus placebo + chemotherapy for early TNBC: exploratory analysis from KEYNOTE-522. J Clin Oncol. 2022;40:16. Abstract 503.

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