Pembrolizumab plus chemotherapy as neoadjuvant treatment of high-risk, early-stage triple-negative breast cancer: results from the phase 1b open-label, multicohort KEYNOTE-173 study
Open accessAbstract
Background The phase Ib KEYNOTE-173 study was conducted to assess the safety and preliminary antitumor activity of neoadjuvant chemotherapy plus pembrolizumab in high-risk, early-stage, non-metastatic triple-negative breast cancer (TNBC).Patients and methods Six pembrolizumab plus chemotherapy regimens were evaluated (cohorts A-F). All cohorts received a pembrolizumab 200-mg run-in dose (cycle 1), then eight cycles of pembrolizumab in combination with a taxane with or without carboplatin for 12 weeks, and then doxorubicin and cyclophosphamide for an additional 12 weeks before surgery. Primary end points were safety and recommended phase II dose (RP2D); secondary end points were pathological complete response (pCR) rate, objective response rate, and event-free and overall survival. Exploratory end points were the relationship between outcome and potential biomarkers, such as tumor programmed death ligand 1 (PD-L1) expression (combined positive score) and stromal tumor-infiltrating lymphocyte levels (sTILs).Results Sixty patients were enrolled between 18 February 2016, and 28 February 2017. Dose-limiting toxicities occurred in 22 patients, most commonly febrile neutropenia (n = 10 across cohorts). Four cohorts (B, C, D, F) did not meet the RP2D threshold; two cohorts did (A, E). The most common grade ≥3 treatment-related adverse event was neutropenia (73%). Immune-mediated adverse events and infusion reactions occurred in 18 patients (30%) and were grade ≥3 in six patients (10%). The pCR rate (ypT0/Tis ypN0) across all cohorts was 60% (range 49%-71%). Twelve-month event-free and overall survival rates ranged from 80% to 100% across cohorts (100% for four cohorts). Higher pre-treatment PD-L1 combined positive score, and pre- and on-treatment sTILs were significantly associated with higher pCR rates (P = 0.0127, 0.0059, and 0.0085, respectively).Conclusion Combination neoadjuvant chemotherapy and pembrolizumab for high-risk, early-stage TNBC showed manageable toxicity and promising antitumor activity. In an exploratory analysis, the pCR rate showed a positive correlation with tumor PD-L1 expression and sTIL levels.Trial registration ClinicalTrials.gov identifier: NCT02622074.
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Immune checkpoint blockade directed against PD-1 or PD-L1 has shown promising results in TNBC, but the overall response rate is less than 20%.
“Immune checkpoint blockade (ICB) directed against programmed death-1 (PD-1) or programmed death-ligand 1 (PD-L1) has shown promising results in TNBC4–6, but the overall response rate of ICB is less than 20%7.”
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Cites
(2016) · Springer eBooks · doi:10.1007/978-3-319-40618-3 · Cited by 17,279 · see citing works
Egner, J. R. (2010) · JAMA · doi:10.1001/jama.2010.1525 · Cited by 6,056 · see citing works
Triple-negative breast cancer: clinical features and patterns of recurrence
Dent, R., Trudeau, M., Pritchard, K. I., Hanna, W. M., Kahn, H. K., Sawka, C. A., Lickley, L. A., Rawlinson, E., Sun, P., & Narod, S. A. (2007) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-06-3045 · Cited by 5,091 · see citing works
Self-citationCortazar, P., Zhang, L., Untch, M., Mehta, K. M., Costantino, J. P., Wolmark, N., Bonnefoi, H. R., Cameron, D., Gianni, L., Valagussa, P., et al. (2014) · The Lancet · doi:10.1016/s0140-6736(13)62422-8 · Cited by 4,777 · see citing works
Foulkes, W. D., Smith, I. E., & Reis-Filho, J. S. (2010) · New England Journal of Medicine · doi:10.1056/nejmra1001389 · Cited by 4,719 · see citing works
Wolff, A. C., Hammond, M. E. H., Hicks, D. G., Dowsett, M., McShane, L. M., Allison, K. H., Allred, D. C., Bartlett, J. M. S., Bilous, M., Fitzgibbons, P. L., et al. (2013) · Journal of Clinical Oncology · doi:10.1200/jco.2013.50.9984 · Cited by 4,029 · see citing works
Salgado, R., Denkert, C., Demaria, S., Sirtaine, N., Klauschen, F., Pruneri, G., Wienert, S., den Eynden, G. V., Baehner, F. L., Penault-Llorca, F. M., et al. (2014) · Annals of Oncology · doi:10.1093/annonc/mdu450 · Cited by 3,142 · see citing works
Self-citationLiedtke, C., Mazouni, C., Hess, K. R., André, F., Tordai, A., Mejia, J. A., Symmans, W. F., Gonzalez-Angulo, A. M., Hennessy, B., Green, M., et al. (2008) · Journal of Clinical Oncology · doi:10.1200/jco.2007.14.4147 · Cited by 2,892 · see citing works
Loi, S., Sirtaine, N., Piette, F., Salgado, R., Viale, G., Eenoo, F. V., Rouas, G., Francis, P. A., Crown, J. P., Hitre, E., et al. (2013) · Journal of Clinical Oncology · doi:10.1200/jco.2011.41.0902 · Cited by 1,634 · see citing works
Self-citationImmunological effects of conventional chemotherapy and targeted anticancer agents
Galluzzi, L., Buqué, A., Kepp, O., Zitvogel, L., & Kroemer, G. (2015) · Cancer Cell · doi:10.1016/j.ccell.2015.10.012 · Cited by 1,530 · see citing works
PD-L1 Expression in Triple-Negative Breast Cancer
Mittendorf, E. A., Philips, A. V., Meric‐Bernstam, F., Qiao, N., Wu, Y., Harrington, S. M., Su, X., Wang, Y., Gonzalez-Angulo, A. M., Akçakanat, A., et al. (2014) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-13-0127 · Cited by 1,394 · see citing works
von Minckwitz, G., Schneeweiß, A., Loibl, S., Salat, C., Denkert, C., Rezai, M., Blohmer, J., Jackisch, C., Paepke, S., Gerber, B., et al. (2014) · The Lancet Oncology · doi:10.1016/s1470-2045(14)70160-3 · Cited by 1,025 · see citing works
Sikov, W. M., Berry, D. A., Perou, C. M., Singh, B., Cirrincione, C., Tolaney, S. M., Kuzma, C. S., Pluard, T., Somlo, G., Port, E. R., et al. (2014) · Journal of Clinical Oncology · doi:10.1200/jco.2014.57.0572 · Cited by 1,017 · see citing works
Loi, S., Drubay, D., Adams, S., Pruneri, G., Francis, P. A., Lacroix-Triki, M., Joensuu, H., Dieci, M. V., Badve, S., Demaria, S., et al. (2019) · Journal of Clinical Oncology · doi:10.1200/jco.18.01010 · Cited by 893 · see citing works
Self-citationClinical relevance of host immunity in breast cancer: from TILs to the clinic
Savas, P., Salgado, R., Denkert, C., Sotiriou, C., Darcy, P. K., Smyth, M. J., & Loi, S. (2016) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2015.215 · Cited by 890 · see citing works
Self-citationAdams, S., Schmid, P., Rugo, H. S., Winer, E. P., Loirat, D., Awada, A., Cescon, D. W., Iwata, H., Campone, M., Nanda, R., et al. (2019) · Annals of Oncology · doi:10.1093/annonc/mdy517 · Cited by 807 · see citing works
Self-citationVariation in the Incidence and Magnitude of Tumor-Infiltrating Lymphocytes in Breast Cancer Subtypes
Stanton, S. E., Adams, S., & Disis, M. L. (2016) · JAMA Oncology · doi:10.1001/jamaoncol.2016.1061 · Cited by 632 · see citing works
Adams, S., Loi, S., Toppmeyer, D., Cescon, D. W., Laurentiis, M. D., Nanda, R., Winer, E. P., Mukai, H., Tamura, K., Armstrong, A. C., et al. (2018) · Annals of Oncology · doi:10.1093/annonc/mdy518 · Cited by 632 · see citing works
Self-citationGhebeh, H., Mohammed, S. F., Al-Omair, A., Qattan, A. T., Lehé, C. L., Al-Qudaihi, G., Elkum, N. B., Alshabanah, M., Amer, S. M. B., Tulbah, A. M., et al. (2006) · Neoplasia · doi:10.1593/neo.05733 · Cited by 612 · see citing works
Kulangara, K., Zhang, N., Corigliano, E., Guerrero, L., Waldroup, S. A., Jaiswal, D., Jansson, M., Shah, S., Hanks, D. A., Wang, J., et al. (2018) · Archives of Pathology & Laboratory Medicine · doi:10.5858/arpa.2018-0043-oa · Cited by 538 · see citing works
Hassett, M. J., O’Malley, A. J., Pakes, J., Newhouse, J. P., & Earle, C. C. (2006) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/djj305 · Cited by 360 · see citing works
Beckers, R., Selinger, C. I., Vilain, R. E., Madore, J., Wilmott, J. S., Harvey, K., Holliday, A., Cooper, C. L., Robbins, E., Gillett, D. J., et al. (2015) · Histopathology · doi:10.1111/his.12904 · Cited by 231 · see citing works
Nanda, R., Liu, M., Yau, C. S. F., Asare, S. M., Hylton, N., Veer, L. V., Perlmutter, J., Wallace, A. M., Chien, A. J., Forero, A., et al. (2017) · Journal of Clinical Oncology · doi:10.1200/jco.2017.35.15_suppl.506 · Cited by 204 · see citing works
Matikas, A., Zerdes, I., Lövrot, J., Richard, F., Sotiriou, C. P., Bergh, J. C. S., Valachis, A., & Foukakis, T. (2019) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-19-1131 · Cited by 114 · see citing works
Self-citationClassical pathology and mutational load of breast cancer – integration of two worlds
Budczies, J., Bockmayr, M. L., Denkert, C., Klauschen, F., Lennerz, J. K., Győrffy, B., Dietel, M., Loibl, S., Weichert, W., & Stenzinger, A. (2015) · The Journal of Pathology Clinical Research · doi:10.1002/cjp2.25 · Cited by 111 · see citing works
Schmid, P., Cortés, J., Dent, R. A., Pusztai, L., McArthur, H. L., Küemmel, S., Bergh, J. C. S., Denkert, C., Park, Y. H., Hui, R., et al. (2019) · Annals of Oncology · doi:10.1093/annonc/mdz394.003 · Cited by 76 · see citing works
Self-citationRashid, N., Koh, H. A., Baca, H. C., Li, Z., Malecha, S., Abidoye, O. O., & Masaquel, A. S. (2015) · Journal of Managed Care & Specialty Pharmacy · doi:10.18553/jmcp.2015.21.10.863 · Cited by 51 · see citing works
Chen, X., Yuan, Y., Garfield, D. H., Wu, J., Huang, O., & Shen, K. (2014) · PLoS ONE · doi:10.1371/journal.pone.0108405 · Cited by 35 · see citing works
Flagged first, then by citations
Research works printed but not linked: 1
- Cortazar P, Zhang L, Untch M, et al. Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis. Lancet. 2014;384:164e172.
Cited by
Sorted by citations
Event-free Survival with Pembrolizumab in Early Triple-Negative Breast Cancer
Schmid, P., Cortes, J., Dent, R., Pusztai, L., McArthur, H., Kümmel, S., Bergh, J., Denkert, C., Park, Y. H., Hui, R., et al. (2022) · New England Journal of Medicine · doi:10.1056/nejmoa2112651 · Cited by 1,274 · see citing works
Self-citationPathogenesis of Triple-Negative Breast Cancer
Derakhshan, F., & Reis-Filho, J. S. (2022) · Annual Review of Pathology: Mechanisms of Disease · doi:10.1146/annurev-pathol-042420-093238 · Cited by 714 · see citing works
Neoadjuvant immune checkpoint blockade: A window of opportunity to advance cancer immunotherapy
Topalian, S. L., Forde, P. M., Emens, L. A., Yarchoan, M., Smith, K. N., & Pardoll, D. M. (2023) · Cancer Cell · doi:10.1016/j.ccell.2023.07.011 · Cited by 317 · see citing works
Ma, S., Zhao, Y., Lee, W. C., Ong, L.-T., Lee, P. L., Jiang, Z., Oguz, G., Niu, Z., Liu, M., Goh, J. Y., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-31764-9 · Cited by 200 · see citing works
A population-level digital histologic biomarker for enhanced prognosis of invasive breast cancer
Amgad, M., Hodge, J. M., Elsebaie, M. A. T., Bodelon, C., Puvanesarajah, S., Gutman, D. A., Siziopikou, K. P., Goldstein, J. A., Gaudet, M. M., Teras, L. R., et al. (2024) · Nature Medicine · doi:10.1038/s41591-023-02643-7 · Cited by 137 · see citing works
Refining patient selection for breast cancer immunotherapy: beyond PD-L1
Kossai, M., Radosevic-Robin, N., & Penault-Llorca, F. (2021) · ESMO Open · doi:10.1016/j.esmoop.2021.100257 · Cited by 36 · see citing works
Clinical benefit of neoadjuvant anti‐PD‐1/PD‐L1 utilization among different tumors
Li, Z., Wu, X., Zhao, Y., Xiao, Y., Zhao, Y., Zhang, T., Li, H., Sha, F., Wang, Y., Deng, L., et al. (2021) · MedComm · doi:10.1002/mco2.61 · Cited by 23 · see citing works
Immunotherapeutic strategies in breast cancer: a clinical update
Zhang, J. Q., & Plitas, G. (2021) · Journal of Surgical Oncology · doi:10.1002/jso.26287 · Cited by 6 · see citing works
- Authors
- Schmid, P., Salgado, R., Park, Y. H., Muñoz-Couselo, E., Kim, S. B., Sohn, J., Im, S.-A., Foukakis, T., Kuemmel, S., Dent, R., Yin, L., Wang, A., Tryfonidis, K., Karantza, V., Cortés, J., & Loi, S.
- Affiliations
- Barts Cancer Institute (GB)
- The University of Melbourne (AU)
- Samsung Medical Center (KR)
- Asan Medical Center (KR)
- Yonsei University (KR)
- Seoul National University (KR)
- Karolinska University Hospital (SE)
- National Cancer Centre Singapore (SG)
- Merck & Co., Inc., Rahway, NJ, USA (United States) (US)
- Vall d'Hebron Institute of Oncology (ES)
- Corresponding author
- Schmid, P.
- ORCID
- Venue
- Annals of Oncology
- Publisher
- Elsevier BV
- Published
- 2020-05
- Volume
- 31
- Issue
- 5
- Pages
- 569-581
- ISSN
- 0923-7534 (ISSN-L)
- OpenAlex
- W3008792561
- Cited by
- 413
- References
- 28
- Citations by year
- 2026: 27 · 2025: 52 · 2024: 60 · 2023: 83 · 2022: 83 · 2021: 74 · 2020: 33 · 2019: 1
- FWCI
- 23.93
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Annals of Oncology (publishedVersion)
- PubMed (publishedVersion)
- Seoul National University Open Repository (Seoul National University) (submittedVersion)
- Funders
- Merck Sharp & Dohme Corp.
- Merck & Co., Inc.
- Merck Sharp and Dohme
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Breast Cancer Treatment Studies
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Health Sciences › Medicine › Oncology › Cancer Treatment and Pharmacology
- Keywords
- triple-negative breast cancer, neoadjuvant therapy, immune checkpoint inhibitors, PD-L1 expression, tumor-infiltrating lymphocytes, pathological complete response, taxanes, carboplatin, doxorubicin, cyclophosphamide, dose-limiting toxicity, immune-related adverse events, early breast cancer, biomarkers, event-free survival
- MeSH terms
- Antineoplastic Combined Chemotherapy Protocols, Humans, Carboplatin, Neoadjuvant Therapy, Antibodies, Monoclonal, Humanized, Triple Negative Breast Neoplasms
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