PELICAN-IPC 2015-016/Oncodistinct-003: A Prospective, Multicenter, Open-Label, Randomized, Non-Comparative, Phase II Study of Pembrolizumab in Combination With Neo Adjuvant EC-Paclitaxel Regimen in HER2-Negative Inflammatory Breast Cancer

Alexandre Bertucci, François Bertucci, Christophe Zemmour, Florence Lerebours, Jean-Yves Pierga, Christelle Levy, Florence Dalenc, Julien Grenier, Thierry Petit, Marguerite Berline, Anthony Gonçalves, Alexandre Bertucci, François Bertucci, Christophe Zemmour, Florence Lerebours, Jean-Yves Pierga, Christelle Levy, Florence Dalenc, Julien Grenier, Thierry Petit, Marguerite Berline, Anthony Gonçalves

Abstract

Inflammatory breast cancer (IBC) is a highly aggressive entity with a poor outcome and relative resistance to treatment. Despite progresses achieved during the last decades, the survival remains significantly lower than non-IBC. Recent clinical trials assessing PD-1/PD-L1 inhibitors showed promising results in non-IBC. Pembrolizumab, an anti-PD-1 monoclonal antibody, revolutionized the treatment of different cancers. Several recent studies suggested a potential interest of targeting the immune system in IBC by revealing a more frequent PD-L1 expression and an enriched immune microenvironment when compared with non-IBC. Here, we describe the rationale and design of PELICAN-IPC 2015-016/Oncodistinct-003 trial, an open-label, randomized, non-comparative, phase II study assessing efficacy, and safety of pembrolizumab in combination with anthracycline-containing neoadjuvant chemotherapy in HER2-negative IBC. The trial is ongoing. The primary endpoint is the pCR rate (ypT0/Tis, ypN0) in overall population and the co-primary endpoint is safety profile during a run-in phase. Key secondary objectives include tolerability, invasive disease-free, event-free and overall survivals, as well as collection of tumor and blood samples for translational research.

Clinical trial registration: https://ichgcp.net/clinical-trials-registry/NCT03515798" title="See in ClinicalTrials.gov">NCT03515798).

Keywords: PDL1; immune checkpoint inhibitor; inflammatory breast cancer; neoadjuvant therapy; pembrolizumab.

Conflict of interest statement

AG reports travel expenses, accommodation, and meeting registration from Astra Zeneca, Pfizer, Roche, and Novartis. The remaining author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2020 Bertucci, Bertucci, Zemmour, Lerebours, Pierga, Levy, Dalenc, Grenier, Petit, Berline and Gonçalves.

Figures

Figure 1
Figure 1
Design of PELICAN-IPC 2015-016/Oncodistinct-003 trial. BC, breast cancer; IBC, inflammatory breast cancer; HR, hormone receptor; pCR, pathological complete response.

References

    1. Chang S, Parker SL, Pham T, Buzdar AU, Hursting SD. Inflammatory breast carcinoma incidence and survival: the surveillance, epidemiology, and end results program of the National Cancer Institute, 1975-1992. Cancer (1998) 82:2366–72. 10.1002/(SICI)1097-0142(19980615)82:12<2366::AID-CNCR10>;2-N
    1. Dawood S, Merajver SD, Viens P, Vermeulen PB, Swain SM, Buchholz TA, et al. International expert panel on inflammatory breast cancer: consensus statement for standardized diagnosis and treatment. Ann Oncol (2011) 22:515–23. 10.1093/annonc/mdq345
    1. Cristofanilli M, Valero V, Buzdar AU, Kau S-W, Broglio KR, Gonzalez-Angulo AM, et al. Inflammatory breast cancer (IBC) and patterns of recurrence: understanding the biology of a unique disease. Cancer (2007) 110:1436–44. 10.1002/cncr.22927
    1. Anderson WF, Chu KC, Chang S. Inflammatory Breast Carcinoma and Noninflammatory Locally Advanced Breast Carcinoma: Distinct Clinicopathologic Entities? JCO (2003) 21:2254–9. 10.1200/JCO.2003.07.082
    1. Hance KW, Anderson WF, Devesa SS, Young HA, Levine PH. Trends in Inflammatory Breast Carcinoma Incidence and Survival: The Surveillance, Epidemiology, and End Results Program at the National Cancer Institute. JNCI: J Natl Cancer Institute (2005) 97:966–75. 10.1093/jnci/dji172
    1. van Uden DJP, Bretveld R, Siesling S, de Wilt JHW, Blanken-Peeters CFJM. Inflammatory breast cancer in the Netherlands; improved survival over the last decades. Breast Cancer Res Treat (2017) 162:365–74. 10.1007/s10549-017-4119-6
    1. Dawood S, Ueno NT, Valero V, Woodward WA, Buchholz TA, Hortobagyi GN, et al. Differences in survival among women with stage III inflammatory and noninflammatory locally advanced breast cancer appear early: A large population-based study. Cancer (2011) 117:1819–26. 10.1002/cncr.25682
    1. Charafe-Jauffret E, Tarpin C, Bardou V-J, Bertucci F, Ginestier C, Braud A-C, et al. Immunophenotypic analysis of inflammatory breast cancers: identification of an’inflammatory signature.’. J Pathol (2004) 202:265–73. 10.1002/path.1515
    1. Ben Hamida A, Labidi IS, Mrad K, Charafe-Jauffret E, Ben Arab S, Esterni B, et al. Markers of subtypes in inflammatory breast cancer studied by immunohistochemistry: Prominent expression of P-cadherin. BMC Cancer (2008) 8:28. 10.1186/1471-2407-8-28
    1. Bieche I. Molecular Profiling of Inflammatory Breast Cancer: Identification of a Poor-Prognosis Gene Expression Signature. Clin Cancer Res (2004) 10:6789–95. 10.1158/1078-0432.CCR-04-0306
    1. McCarthy NJ, Yang X, Linnoila IR, Merino MJ, Hewitt SM, Parr AL, et al. Microvessel density, expression of estrogen receptor alpha, MIB-1, p53, and c-erbB-2 in inflammatory breast cancer. Clin Cancer Res (2002) 8:3857–62.
    1. Colpaert CG, Vermeulen PB, Benoy I, Soubry A, van Roy F, van Beest P, et al. Inflammatory breast cancer shows angiogenesis with high endothelial proliferation rate and strong E-cadherin expression. Br J Cancer (2003) 88:718–25. 10.1038/sj.bjc.6600807
    1. Bonnier P, Charpin C, Lejeune C, Romain S, Tubiana N, Beedassy B, et al. Inflammatory carcinomas of the breast: A clinical, pathological, or a clinical and pathological definition? Int J Cancer (1995) 62:382–5. 10.1002/ijc.2910620404
    1. Amparo RS, Angel CDM, Ana LH, Antonio LC, Vicente MS, Carlos F-M, et al. Inflammatory Breast Carcinoma: Pathological or Clinical Entity? Breast Cancer Res Treat (2000) 64:269–73. 10.1023/A:1026512722789
    1. Bertucci F, Finetti P, Vermeulen P, Van Dam P, Dirix L, Birnbaum D, et al. Genomic profiling of inflammatory breast cancer: a review. Breast (2014) 23:538–45. 10.1016/j.breast.2014.06.008
    1. Van Laere SJ, Ueno NT, Finetti P, Vermeulen P, Lucci A, Robertson FM, et al. Uncovering the molecular secrets of inflammatory breast cancer biology: an integrated analysis of three distinct affymetrix gene expression datasets. Clin Cancer Res (2013) 19:4685–96. 10.1158/1078-0432.CCR-12-2549
    1. Rybczynska AA, Boersma HH, de Jong S, Gietema JA, Noordzij W, Dierckx RAJO, et al. Avenues to molecular imaging of dying cells: Focus on cancer. Med Res Rev (2018) 38:1713–68. 10.1002/med.21495
    1. Viens P, Tarpin C, Roche H, Bertucci F. Systemic therapy of inflammatory breast cancer from high-dose chemotherapy to targeted therapies: the French experience. Cancer (2010) 116:2829–36. 10.1002/cncr.25168
    1. Gianni L, Eiermann W, Semiglazov V, Manikhas A, Lluch A, Tjulandin S, et al. Neoadjuvant chemotherapy with trastuzumab followed by adjuvant trastuzumab versus neoadjuvant chemotherapy alone, in patients with HER2-positive locally advanced breast cancer (the NOAH trial): a randomised controlled superiority trial with a parallel HER2-negative cohort. Lancet (2010) 375:377–84. 10.1016/S0140-6736(09)61964-4
    1. Gianni L, Pienkowski T, Im Y-H, Roman L, Tseng L-M, Liu M-C, et al. Efficacy and safety of neoadjuvant pertuzumab and trastuzumab in women with locally advanced, inflammatory, or early HER2-positive breast cancer (NeoSphere): a randomised multicentre, open-label, phase 2 trial. Lancet Oncol (2012) 13:25–32. 10.1016/S1470-2045(11)70336-9
    1. Chan A, Delaloge S, Holmes FA, Moy B, Iwata H, Harvey VJ, et al. Neratinib after trastuzumab-based adjuvant therapy in patients with HER2-positive breast cancer (ExteNET): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol (2016) 17:367–77. 10.1016/S1470-2045(15)00551-3
    1. von Minckwitz G, Huang C-S, Mano MS, Loibl S, Mamounas EP, Untch M, et al. Trastuzumab Emtansine for Residual Invasive HER2-Positive Breast Cancer. N Engl J Med (2019) 380:617–28. 10.1056/NEJMoa1814017
    1. Pierga J-Y, Petit T, Delozier T, Ferrero J-M, Campone M, Gligorov J, et al. Neoadjuvant bevacizumab, trastuzumab, and chemotherapy for primary inflammatory HER2-positive breast cancer (BEVERLY-2): an open-label, single-arm phase 2 study. Lancet Oncol (2012) 13:375–84. 10.1016/S1470-2045(12)70049-9
    1. Bertucci F, Fekih M, Autret A, Petit T, Dalenc F, Levy C, et al. Bevacizumab plus neoadjuvant chemotherapy in patients with HER2-negative inflammatory breast cancer (BEVERLY-1): a multicentre, single-arm, phase 2 study. Lancet Oncol (2016) 17:600–11. 10.1016/S1470-2045(16)00011-5
    1. Matsuda N, Wang X, Lim B, Krishnamurthy S, Alvarez RH, Willey JS, et al. Safety and Efficacy of Panitumumab Plus Neoadjuvant Chemotherapy in Patients With Primary HER2-Negative Inflammatory Breast Cancer. JAMA Oncol (2018) 4:1207–13. 10.1001/jamaoncol.2018.1436
    1. Denkert C, Loibl S, Noske A, Roller M, Müller BM, Komor M, et al. Tumor-Associated Lymphocytes As an Independent Predictor of Response to Neoadjuvant Chemotherapy in Breast Cancer. J Clin Oncol (2010) 28:105–13. 10.1200/JCO.2009.23.7370
    1. Loi S, Michiels S, Salgado R, Sirtaine N, Jose V, Fumagalli D, et al. Tumor infiltrating lymphocytes are prognostic in triple negative breast cancer and predictive for trastuzumab benefit in early breast cancer: results from the FinHER trial. Ann Oncol (2014) 25:1544–50. 10.1093/annonc/mdu112
    1. Ali HR, Provenzano E, Dawson S-J, Blows FM, Liu B, Shah M, et al. Association between CD8+ T-cell infiltration and breast cancer survival in 12 439 patients. Ann Oncol (2014) 25:1536–43. 10.1093/annonc/mdu191
    1. Rody A, Holtrich U, Pusztai L, Liedtke C, Gaetje R, Ruckhaeberle E, et al. T-cell metagene predicts a favorable prognosis in estrogen receptor-negative and HER2-positive breast cancers. Breast Cancer Res (2009) 11:R15. 10.1186/bcr2234
    1. Teschendorff AE, Miremadi A, Pinder SE, Ellis IO, Caldas C. An immune response gene expression module identifies a good prognosis subtype in estrogen receptor negative breast cancer. Genome Biol (2007) 8:R157. 10.1186/gb-2007-8-8-r157
    1. Sabatier R, Finetti P, Mamessier E, Raynaud S, Cervera N, Lambaudie E, et al. Kinome expression profiling and prognosis of basal breast cancers. Mol Cancer (2011) 10:86. 10.1186/1476-4598-10-86
    1. Sabatier R, Finetti P, Cervera N, Lambaudie E, Esterni B, Mamessier E, et al. A gene expression signature identifies two prognostic subgroups of basal breast cancer. Breast Cancer Res Treat (2011) 126:407–20. 10.1007/s10549-010-0897-9
    1. Demaria S, Volm MD, Shapiro RL, Yee HT, Oratz R, Formenti SC, et al. Development of tumor-infiltrating lymphocytes in breast cancer after neoadjuvant paclitaxel chemotherapy. Clin Cancer Res (2001) 7:3025–30.
    1. Ladoire S, Mignot G, Dabakuyo S, Arnould L, Apetoh L, Rébé C, et al. In situ immune response after neoadjuvant chemotherapy for breast cancer predicts survival. J Pathol (2011) 224:389–400. 10.1002/path.2866
    1. Ahmadzadeh M, Johnson LA, Heemskerk B, Wunderlich JR, Dudley ME, White DE, et al. Tumor antigen–specific CD8 T cells infiltrating the tumor express high levels of PD-1 and are functionally impaired. Blood (2009) 114:1537–44. 10.1182/blood-2008-12-195792
    1. Dong H, Strome SE, Salomao DR, Tamura H, Hirano F, Flies DB, et al. Tumor-associated B7-H1 promotes T-cell apoptosis: A potential mechanism of immune evasion. Nat Med (2002) 8:793–800. 10.1038/nm730
    1. Francisco LM, Salinas VH, Brown KE, Vanguri VK, Freeman GJ, Kuchroo VK, et al. PD-L1 regulates the development, maintenance, and function of induced regulatory T cells. J Exp Med (2009) 206:3015–29. 10.1084/jem.20090847
    1. Hamel KM, Cao Y, Wang Y, Rodeghero R, Kobezda T, Chen L, et al. B7-H1 expression on non-B and non-T cells promotes distinct effects on T- and B-cell responses in autoimmune arthritis. Eur J Immunol (2010) 40:3117–27. 10.1002/eji.201040690
    1. Zou W, Chen L. Inhibitory B7-family molecules in the tumour microenvironment. Nat Rev Immunol (2008) 8:467–77. 10.1038/nri2326
    1. Iwai Y, Ishida M, Tanaka Y, Okazaki T, Honjo T, Minato N. Involvement of PD-L1 on tumor cells in the escape from host immune system and tumor immunotherapy by PD-L1 blockade. Proc Natl Acad Sci (2002) 99:12293–7. 10.1073/pnas.192461099
    1. Reiss KA, Forde PM, Brahmer JR. Harnessing the power of the immune system via blockade of PD-1 and PD-L1: a promising new anticancer strategy. Immunotherapy (2014) 6:459–75. 10.2217/imt.14.9
    1. Ghebeh H, Mohammed S, Al-Omair A, Qattant A, Lehe C, Al-Qudaihi G, et al. The B7-H1 (PD-L1) T Lymphocyte-Inhibitory Molecule Is Expressed in Breast Cancer Patients with Infiltrating Ductal Carcinoma: Correlation with Important High-Risk Prognostic Factors. Neoplasia (2006) 8:190–8. 10.1593/neo.05733
    1. Ghebeh H, Tulbah A, Mohammed S, ElKum N, Amer SMB, Al-Tweigeri T, et al. Expression of B7-H1 in breast cancer patients is strongly associated with high proliferative Ki-67-expressing tumor cells. Int J Cancer (2007) 121:751–8. 10.1002/ijc.22703
    1. Ghebeh H, Barhoush E, Tulbah A, Elkum N, Al-Tweigeri T, Dermime S. FOXP3+ Tregs and B7-H1+/PD-1+T lymphocytes co-infiltrate the tumor tissues of high-risk breast cancer patients: Implication for immunotherapy. BMC Cancer (2008) 8:57. 10.1186/1471-2407-8-57
    1. Schalper KA, Velcheti V, Carvajal D, Wimberly H, Brown J, Pusztai L, et al. In Situ Tumor PD-L1 mRNA Expression Is Associated with Increased TILs and Better Outcome in Breast Carcinomas. Clin Cancer Res (2014) 20:2773–82. 10.1158/1078-0432.CCR-13-2702
    1. Soliman H, Khalil F, Antonia S. PD-L1 Expression Is Increased in a Subset of Basal Type Breast Cancer Cells. PloS One (2014) 9:e88557. 10.1371/journal.pone.0088557
    1. Mittendorf EA, Philips AV, Meric-Bernstam F, Qiao N, Wu Y, Harrington S, et al. PD-L1 Expression in Triple-Negative Breast Cancer. Cancer Immunol Res (2014) 2:361–70. 10.1158/2326-6066.CIR-13-0127
    1. Sabatier R, Finetti P, Mamessier E, Adelaide J, Chaffanet M, Ali HR, et al. Prognostic and predictive value of PDL1 expression in breast cancer. Oncotarget (2015) 6:5449–64. 10.18632/oncotarget.3216
    1. Wimberly H, Brown JR, Schalper K, Haack H, Silver MR, Nixon C, et al. PD-L1 Expression Correlates with Tumor-Infiltrating Lymphocytes and Response to Neoadjuvant Chemotherapy in Breast Cancer. Cancer Immunol Res (2015) 3:326–32. 10.1158/2326-6066.CIR-14-0133
    1. Bertucci F, Ueno NT, Finetti P, Vermeulen P, Lucci A, Robertson FM, et al. Gene expression profiles of inflammatory breast cancer: correlation with response to neoadjuvant chemotherapy and metastasis-free survival. Ann Oncol (2014) 25:358–65. 10.1093/annonc/mdt496
    1. Bertucci F, Finetti P, Colpaert C, Mamessier E, Parizel M, Dirix L, et al. PDL1 expression in inflammatory breast cancer is frequent and predicts for the pathological response to chemotherapy. Oncotarget (2015) 6:13506–19. 10.18632/oncotarget.3642
    1. Arias-Pulido H, Cimino-Mathews A, Chaher N, Qualls C, Joste N, Colpaert C, et al. The combined presence of CD20 + B cells and PD-L1 + tumor-infiltrating lymphocytes in inflammatory breast cancer is prognostic of improved patient outcome. Breast Cancer Res Treat (2018) 171:273–82. 10.1007/s10549-018-4834-7
    1. Van Berckelaer C, Rypens C, van Dam P, Pouillon L, Parizel M, Schats KA, et al. Infiltrating stromal immune cells in inflammatory breast cancer are associated with an improved outcome and increased PD-L1 expression. Breast Cancer Res (2019) 21:28. 10.1186/s13058-019-1108-1
    1. Liang X, Vacher S, Boulai A, Bernard V, Baulande S, Bohec M, et al. Targeted next-generation sequencing identifies clinically relevant somatic mutations in a large cohort of inflammatory breast cancer. Breast Cancer Res (2018) 20:88. 10.1186/s13058-018-1007-x
    1. Bertucci F, Rypens C, Finetti P, Guille A, Adélaïde J, Monneur A, et al. NOTCH and DNA repair pathways are more frequently targeted by genomic alterations in inflammatory than in non-inflammatory breast cancers. Mol Oncol (2019) 13(3): 504–19. 10.1002/1878-0261.12621
    1. Planes-Laine G, Rochigneux P, Bertucci F, Chrétien A-S, Viens P, Sabatier R, et al. PD-1/PD-L1 Targeting in Breast Cancer: The First Clinical Evidences Are Emerging. A Literature Review. Cancers (2019) 11:1033. 10.3390/cancers11071033
    1. Cortés J, Lipatov O, Im S-A, Gonçalves A, Lee KS, Schmid P, et al. KEYNOTE-119: Phase III study of pembrolizumab (pembro) versus single-agent chemotherapy (chemo) for metastatic triple negative breast cancer (mTNBC). Ann Oncol (2019) 30:v859–60. 10.1093/annonc/mdz394.010
    1. Zitvogel L, Apetoh L, Ghiringhelli F, André F, Tesniere A, Kroemer G. The anticancer immune response: indispensable for therapeutic success? J Clin Invest (2008) 118:1991–2001. 10.1172/JCI35180
    1. Emens LA, Middleton G. The Interplay of Immunotherapy and Chemotherapy: Harnessing Potential Synergies. Cancer Immunol Res (2015) 3:436–43. 10.1158/2326-6066.CIR-15-0064
    1. Mattarollo SR, Loi S, Duret H, Ma Y, Zitvogel L, Smyth MJ. Pivotal Role of Innate and Adaptive Immunity in Anthracycline Chemotherapy of Established Tumors. Cancer Res (2011) 71:4809–20. 10.1158/0008-5472.CAN-11-0753
    1. Zhu S, Waguespack M, Barker SA, Li S. Doxorubicin Directs the Accumulation of Interleukin-12 Induced IFN into Tumors for Enhancing STAT1 Dependent Antitumor Effect. Clin Cancer Res (2007) 13:4252–60. 10.1158/1078-0432.CCR-06-2894
    1. Ma Y, Aymeric L, Locher C, Mattarollo SR, Delahaye NF, Pereira P, et al. Contribution of IL-17–producing γδ T cells to the efficacy of anticancer chemotherapy. J Exp Med (2011) 208:491–503. 10.1084/jem.20100269
    1. Ma Y, Adjemian S, Mattarollo SR, Yamazaki T, Aymeric L, Yang H, et al. Anticancer Chemotherapy-Induced Intratumoral Recruitment and Differentiation of Antigen-Presenting Cells. Immunity (2013) 38:729–41. 10.1016/j.immuni.2013.03.003
    1. Apetoh L, Mignot G, Panaretakis T, Kroemer G, Zitvogel L. Immunogenicity of anthracyclines: moving towards more personalized medicine. Trends Mol Med (2008) 14:141–51. 10.1016/j.molmed.2008.02.002
    1. Galluzzi L, Senovilla L, Zitvogel L, Kroemer G. The secret ally: immunostimulation by anticancer drugs. Nat Rev Drug Discovery (2012) 11:215–33. 10.1038/nrd3626
    1. Black M, Barsoum IB, Truesdell P, Cotechini T, Macdonald-Goodfellow SK, Petroff M, et al. Activation of the PD-1/PD-L1 immune checkpoint confers tumor cell chemoresistance associated with increased metastasis. Oncotarget (2016) 7:10557–67. 10.18632/oncotarget.7235
    1. Rios-Doria J, Durham N, Wetzel L, Rothstein R, Chesebrough J, Holoweckyj N, et al. Doxil Synergizes with Cancer Immunotherapies to Enhance Antitumor Responses in Syngeneic Mouse Models. Neoplasia (2015) 17:661–70. 10.1016/j.neo.2015.08.004
    1. Schmid P, Chui SY, Emens LA. Atezolizumab and Nab-Paclitaxel in Advanced Triple-Negative Breast Cancer. Reply. N Engl J Med (2019) 380:987–8. 10.1056/NEJMc1900150
    1. Cortes J, Cescon DW, Rugo HS, Nowecki Z, Im S-A, Yusof MM, et al. KEYNOTE-355: Randomized, double-blind, phase III study of pembrolizumab + chemotherapy versus placebo + chemotherapy for previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer. JCO (2020) 38:1000–0. 10.1200/JCO.2020.38.15_suppl.1000
    1. Miles DW, Gligorov J, André F, Cameron D, Schneeweiss A, Barrios CH, et al. LBA15 Primary results from IMpassion131, a double-blind placebo-controlled randomised phase III trial of first-line paclitaxel (PAC) ± atezolizumab (atezo) for unresectable locally advanced/metastatic triple-negative breast cancer (mTNBC). Ann Oncol (2020) 31:S1147–8. 10.1016/j.annonc.2020.08.2243
    1. Cortés J, André F, Gonçalves A, Kümmel S, Martín M, Schmid P, et al. IMpassion132 Phase III trial: atezolizumab and chemotherapy in early relapsing metastatic triple-negative breast cancer. Future Oncol (London England) (2019) 15:1951–61. 10.2217/fon-2019-0059
    1. Nanda R, Liu MC, Yau C, Shatsky R, Pusztai L, Wallace A, et al. Effect of Pembrolizumab Plus Neoadjuvant Chemotherapy on Pathologic Complete Response in Women With Early-Stage Breast Cancer: An Analysis of the Ongoing Phase 2 Adaptively Randomized I-SPY2 Trial. JAMA Oncol (2020) 15:1951–61. 10.1001/jamaoncol.2019.6650
    1. Schmid P, Cortes J, Pusztai L, McArthur H, Kümmel S, Bergh J, et al. Pembrolizumab for Early Triple-Negative Breast Cancer. N Engl J Med (2020) 382:810–21. 10.1056/NEJMoa1910549
    1. Harbeck N, Zhang H, Barrios CH, Saji S, Jung KH, Hegg R, et al. LBA11 IMpassion031: Results from a phase III study of neoadjuvant (neoadj) atezolizumab + chemotherapy in early triple-negative breast cancer (TNBC). Ann Oncol (2020) 31:S1144. 10.1016/j.annonc.2020.08.2239
    1. Loibl S, Untch M, Burchardi N, Huober J, Sinn BV, Blohmer J-U, et al. A randomised phase II study investigating durvalumab in addition to an anthracycline taxane-based neoadjuvant therapy in early triple-negative breast cancer: clinical results and biomarker analysis of GeparNuevo study. Ann Oncol (2019) 30:1279–88. 10.1093/annonc/mdz158
    1. Gianni L, Huang C-S, Egle D, Bermejo B, Zamagni C, Thill M, et al. Abstract GS3-04: Pathologic complete response (pCR) to neoadjuvant treatment with or without atezolizumab in triple negative, early high-risk and locally advanced breast cancer. NeoTRIPaPDL1 Michelangelo randomized study. In: General Session Abstracts. San Antonio breast cancer symposium: American Association for Cancer Research; (2020). p. GS3–04-GS3-04. 10.1158/1538-7445.SABCS19-GS3-04

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