Surgical Outcomes After Neoadjuvant Pembrolizumab Plus Chemotherapy for Triple-Negative Breast Cancer: Results from the Randomized, Placebo-Controlled Phase 3 KEYNOTE-522 Study

Kuemmel S, Fasching P, Schmid P, Harbeck N, Takahashi M, Untch M, Boileau JF, Cortes J, Dent R, O’Shaughnessy J, Pusztai L, Foukakis T, Park YH, Hui R, Cardoso F, Denkert C, Jia L, Pan W, Karantza V, McArthur H (2026)

Publication Type: Journal article

Publication year: 2026

Journal

DOI: 10.1245/s10434-026-19121-2

Abstract

Purpose: We prospectively evaluated surgical outcomes following neoadjuvant pembrolizumab or placebo added to neoadjuvant chemotherapy among participants with early-stage triple-negative breast cancer (TNBC) in the phase 3 KEYNOTE-522 study (NCT03036488). Methods: Participants with previously untreated, early-stage TNBC (AJCC stage T1c N1–2 or T2–4 N0–2) were randomized 2:1 to neoadjuvant pembrolizumab/placebo plus paclitaxel-carboplatin for 4 cycles, followed by pembrolizumab/placebo plus doxorubicin/epirubicin and cyclophosphamide for 4 cycles. After definitive surgery, participants received adjuvant pembrolizumab/placebo Q3W for 9 cycles. Surgery type and timing, nodal status postsurgery, and adverse events within 30 days following surgery were recorded. Results: Among 1,174 randomized participants (pembrolizumab plus chemotherapy, n = 784; placebo plus chemotherapy, n = 390), similar proportions underwent breast-conserving surgery (45.2% vs. 45.6%) and mastectomy (44.0% vs. 42.6%). Median (10th‒90th percentile) time from end of on-study neoadjuvant treatment to surgery was 1.2 (0.9‒1.9) months in the pembrolizumab plus chemotherapy group and 1.2 (0.9‒1.7) months in the placebo plus chemotherapy group. Median (10th‒90th percentile) time from surgery to adjuvant pembrolizumab/placebo was 2.6 (1.0‒3.9) months in the pembrolizumab plus chemotherapy group and 2.7 (1.1‒4.0) months in the placebo plus chemotherapy group. The only AE occurring in ≥5% of participants between 0 and 30 days postsurgery was procedural pain (7.0% vs. 5.8%). The rate of pathological complete nodal response at surgery was 76.7% in the pembrolizumab plus chemotherapy group versus 69.9% in the placebo plus chemotherapy group. Conclusions: These findings show that adding neoadjuvant pembrolizumab to chemotherapy had no adverse impact on surgical outcomes (including type, timing, and safety). Trial registration ClinicalTrials.gov, NCT03036488 https://www.clinicaltrials.gov/study/NCT03036488

Authors with CRIS profile

Additional Organisation(s)

Involved external institutions

Kliniken Essen-Mitte Germany (DE) Queen Mary University of London United Kingdom (GB) Klinikum der Universität München (LMU Klinikum) Germany (DE) Hokkaido University Hospital / 北海道大学病院 Japan (JP) HELIOS Kliniken Germany (DE) McGill University Canada (CA) PANGAEA Oncology S.A. Spain (ES) Duke-NUS Medical School / 杜克—国大医学研究生院 Singapore (SG) Texas Oncology United States (USA) (US) Yale University United States (USA) (US) Karolinska University Hospital / Karolinska Universitetssjukhuset Sweden (SE) Sungkyunkwan University (SKKU) Korea, Republic of (KR) Westmead Hospital Australia (AU) Champalimaud Foundation / Fundação Champalimaud Portugal (PT) Philipps-Universität Marburg Germany (DE) Merck & Co., Inc. / Merck Sharp & Dohme Corp (MSD) United States (USA) (US) University of Texas Southwestern Medical Center (UT Southwestern) United States (USA) (US)

How to cite

APA:

Kuemmel, S., Fasching, P., Schmid, P., Harbeck, N., Takahashi, M., Untch, M.,... McArthur, H. (2026). Surgical Outcomes After Neoadjuvant Pembrolizumab Plus Chemotherapy for Triple-Negative Breast Cancer: Results from the Randomized, Placebo-Controlled Phase 3 KEYNOTE-522 Study. Annals of Surgical Oncology. https://doi.org/10.1245/s10434-026-19121-2

MLA:

Kuemmel, Sherko, et al. "Surgical Outcomes After Neoadjuvant Pembrolizumab Plus Chemotherapy for Triple-Negative Breast Cancer: Results from the Randomized, Placebo-Controlled Phase 3 KEYNOTE-522 Study." Annals of Surgical Oncology (2026).

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