Immunotherapy in the neoadjuvant treatment of triple-negative breast cancer: an interim analysis of a pembrolizumab-based regimen in clinical practice in Moscow

BACKGROUND: In the KEYNOTE-522 trial, adding pembrolizumab to neoadjuvant chemotherapy improved the pathological complete response (pCR) rate, event-free survival and overall survival in patients with early triple-negative breast cancer (TNBC). Data on whether these results can be reproduced in Russian clinical practice are limited.

AIM: To assess the tolerability of chemoimmunotherapy and the pCR rate when pembrolizumab is added to neoadjuvant chemotherapy for TNBC in routine clinical practice in Moscow.

METHODS: We retrospectively analysed data on 152 patients with TNBC who received neoadjuvant chemoimmunotherapy in outpatient cancer care centres in Moscow. The interim analysis (data cut-off March 2026) included 58 patients who had completed the neoadjuvant phase. The primary endpoint was the pCR rate in operated patients; we also assessed the distribution of residual cancer burden (RCB) classes, the effect of the carboplatin schedule (1q1w vs 1q3w), treatment completeness and tolerability.

RESULTS: Median age was 46 years; regional lymph node involvement was present in 79.3 % of patients, stage III disease in 55.2 % and BRCA1/2 mutations in 29.3 %; a weekly carboplatin schedule was used in 75.9 %. Surgery was performed in 56 (96.6 %) patients. pCR was achieved in 78.6 % (95 % confidence interval (CI) 66.2–87.3) of operated patients and in 75.9 % (95 % CI 63.5–85.0) of the analysis set. The pCR rate was 81.0 % with weekly carboplatin and 71.4 % with every-3-week carboplatin (odds ratio (OR) 1.70; 95 % CI 0.42–6.84; p = 0.470); after stratification by stage the difference almost disappeared (Mantel–Haenszel OR 1.20; p = 0.913). None of the factors studied was significantly associated with pCR. The full neoadjuvant course of pembrolizumab was completed by 72.4 % of patients; grade 3 or higher adverse events were reported in 36.8 %.

CONCLUSION: Neoadjuvant chemoimmunotherapy with pembrolizumab in routine clinical practice in Moscow is associated with a high pCR rate despite a less favourable baseline profile than in the KEYNOTE-522 population. These interim results need confirmation in the full cohort and assessment of long-term outcomes. The regimen used – four cycles of doxorubicin + cyclophosphamide followed by paclitaxel with carboplatin, with pembrolizumab given only in the neoadjuvant phase – showed a high pCR rate and acceptable tolerability.

1. Grechukhina K.S., Zhukova L.G. Immunotherapy in combination with chemotherapy for triple-negative breast cancer – the first “targeted” therapy, but only for the “targeted” population. Sovremennaya onkologiya = Journal of Modern Oncology 2019;21(3):33–7. (In Russ.). DOI: 10.26442/18151434.2019.3.190655

2. Zhukova L.G. Breast cancer with triple-negative phenotype in the Russian population of patients. Clinical and morphological features. Voprosy onkologii = Oncology Issues 2015;61(2):189–94. (In Russ.).

3. Dent R., Trudeau M., Pritchard K.I. et al. Triple-negative breast cancer: clinical features and patterns of recurrence. Clin Cancer Res 2007;13(15):4429–34. DOI: 10.1158/1078-0432.CCR-06-3045

4. Schmid P., Adams S., Rugo H.S. et al. Atezolizumab and nabpaclitaxel in advanced triple-negative breast cancer. N Engl J Med 2018;379(22):2108–21. DOI: 10.1056/NEJMoa1809615

5. Li Z.Y., Zhang Z., Cao X.Z. et al. Platinum-based neoadjuvant chemotherapy for triple-negative breast cancer: a systematic review and meta-analysis. J Int Med Res 2020;48(10):300060520964340. DOI: 10.1177/0300060520964340

6. Spring L.M., Fell G., Arfe A. et al. Pathological complete response after neoadjuvant chemotherapy and impact on breast cancer recurrence and survival: a comprehensive meta-analysis. Clin Cancer Res 2020;26(12):2838–48. DOI: 10.1158/1078-0432.CCR-19-3492

7. Loi S., Drubay D., Adams S. et al. Tumor-infiltrating lymphocytes and prognosis: a pooled individual patient analysis of early-stage triple-negative breast cancers. J Clin Oncol 2019;37(7):559–69. DOI: 10.1200/JCO.18.01010

8. Schmid P., Cortes J., Pusztai L. et al. Pembrolizumab for early triple-negative breast cancer. N Engl J Med 2020;382(9):810–21. DOI: 10.1056/NEJMoa1910549

9. 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):1981–91. DOI: 10.1056/NEJMoa2409932

10. Landry K.K., Lyon J.L., Victoria K.E. et al. Weekly vs every-3-week carboplatin with weekly paclitaxel in neoadjuvant chemotherapy for triple-negative breast cancer: a retrospective analysis. Breast Cancer (Dove Med Press) 2022;14:63–70. DOI: 10.2147/BCTT.S342635

11. Satterfield K., Berger M., Reed A. et al. Impact of carboplatin schedule on pCR in a modified KEYNOTE-522 regimen with dose-dense AC for triple negative breast cancer. Oncologist 2025;30(11):oyaf372. DOI: 10.1093/oncolo/oyaf372

12. Schmid P., Cortes J., Dent R. et al. KEYNOTE-522 final analysis: event-free and overall survival with neoadjuvant pembrolizumab plus chemotherapy followed by adjuvant pembrolizumab in early-stage triple-negative breast cancer. J Clin Oncol 2026;44(Suppl. 16):507

13. Cherifi F., Cabel L., Bousrih C. et al. 238MO PROMENADE: PembROlizuMab for early triple negative ER-low breast caNcer, reAl worlD frEnch cohort. Ann Oncol 2024;35(Suppl. 2):S312–3. DOI: 10.1016/j.annonc.2024.08.181

14. Rached L., Peyre-Pradat F., Spotti M. et al. Real-world safety and effectiveness of neoadjuvant chemotherapy combination with pembrolizumab in triple-negative breast cancer. ESMO Real World Data Digit Oncol 2024;5:100061. DOI: 10.1016/j.esmorw.2024.100061

15. Dent R., Cortes J., Pusztai L. et al. Neoadjuvant pembrolizumab plus chemotherapy/adjuvant pembrolizumab for early-stage triple-negative breast cancer: quality-of-life results from the randomized KEYNOTE-522 study. J Natl Cancer Inst 2024;116(10):1654–63. DOI: 10.1093/jnci/djae129