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Role of Immunotherapy in Early- and Late-Stage Triple-Negative Breast Cancer

  • Stefania Morganti
    Affiliations
    Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA

    Breast Oncology Program, Dana-Farber Brigham Cancer Center, Boston, MA, USA

    Harvard Medical School, Boston, MA, USA

    Broad Institute of MIT and Harvard, Boston, MA, USA

    Department of Oncology and Hemato-Oncology, University of Milan, Istituto Europeo di Oncologia, Milan, Italy
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  • Sara M. Tolaney
    Correspondence
    Corresponding author. Dana-Farber Cancer Institute, 450 Brookline Ave., Boston, MA 02215.
    Affiliations
    Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA

    Breast Oncology Program, Dana-Farber Brigham Cancer Center, Boston, MA, USA

    Harvard Medical School, Boston, MA, USA
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      References

        • Drake C.G.
        • Lipson E.J.
        • Brahmer J.R.
        Breathing new life into immunotherapy: review of melanoma, lung and kidney cancer.
        Nat Rev Clin Oncol. 2014; 11: 24-37
        • Bianchini G.
        • De Angelis C.
        • Licata L.
        • et al.
        Treatment landscape of triple-negative breast cancer - expanded options, evolving needs.
        Nat Rev Clin Oncol. 2022; 19: 91-113
        • Nanda R.
        • Chow L.Q.M.
        • Dees E.C.
        • et al.
        Pembrolizumab in patients with advanced triple-negative breast cancer: Phase Ib KEYNOTE-012 study.
        J Clin Oncol. 2016; 34: 2460-2467
        • Adams S.
        • Schmid P.
        • Rugo H.S.
        • et al.
        Pembrolizumab monotherapy for previously treated metastatic triple-negative breast cancer: cohort A of the phase II KEYNOTE-086 study.
        Ann Oncol. 2019; 30: 397-404
        • Dirix L.Y.
        • Takacs I.
        • Jerusalem G.
        • et al.
        Avelumab, an anti-PD-L1 antibody, in patients with locally advanced or metastatic breast cancer: a phase 1b JAVELIN Solid Tumor study.
        Breast Cancer Res Treat. 2018; 167: 671-686
        • Emens L.A.
        • Cruz C.
        • Eder J.P.
        • et al.
        Long-term clinical outcomes and biomarker analyses of atezolizumab therapy for patients with metastatic triple-negative breast cancer: A phase 1 study.
        JAMA Oncol. 2019; 5: 74-82
        • Schmid P.
        • Cortes J.
        • Pusztai L.
        • et al.
        Pembrolizumab for early triple-negative breast cancer.
        N Engl J Med. 2020; 382: 810-821
        • Cortes J.
        • Cescon D.W.
        • Rugo H.S.
        • et al.
        Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer (KEYNOTE-355): a randomised, placebo-controlled, double-blind, phase 3 clinical trial.
        Lancet. 2020; 396: 1817-1828
        • Burstein H.J.
        • Curigliano G.
        • Thürlimann B.
        • et al.
        Customizing local and systemic therapies for women with early breast cancer: the St. Gallen International Consensus Guidelines for treatment of early breast cancer 2021.
        Ann Oncol. 2021; 32: 1216-1235
        • 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: 164-172
        • Schmid P.
        • Cortes J.
        • Dent R.
        • et al.
        VP7-2021: KEYNOTE-522: Phase III study of neoadjuvant pembrolizumab + chemotherapy vs. placebo + chemotherapy, followed by adjuvant pembrolizumab vs. placebo for early-stage TNBC.
        Ann Oncol. 2021; 32: 1198-1200
        • Loibl S.
        • Untch M.
        • Burchardi N.
        • 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: 1279-1288
        • Loibl S.
        • Schneeweiss A.
        • Huober J.B.
        • et al.
        Durvalumab improves long-term outcome in TNBC: results from the phase II randomized GeparNUEVO study investigating neodjuvant durvalumab in addition to an anthracycline/taxane based neoadjuvant chemotherapy in early triple-negative breast cancer (TNBC).
        J Clin Oncol. 2021; 39: 506
        • Gianni L.
        • Huang C.S.
        • Egle D.
        • et al.
        Pathologic complete response (pCR) to neoadjuvant treatment with or without atezolizumab in triple-negative, early high-risk and locally advanced breast cancer: NeoTRIP Michelangelo randomized study.
        Ann Oncol. 2022; 33: 534-543
        • Mittendorf E.A.
        • Zhang H.
        • Barrios C.H.
        • et al.
        Neoadjuvant atezolizumab in combination with sequential nab-paclitaxel and anthracycline-based chemotherapy versus placebo and chemotherapy in patients with early-stage triple-negative breast cancer (IMpassion031): a randomised, double-blind, phase 3 trial.
        Lancet. 2020; 396: 1090-1100
        • Hurvitz S.A.
        • McAndrew N.P.
        • Bardia A.
        • et al.
        A careful reassessment of anthracycline use in curable breast cancer.
        NPJ Breast Cancer. 2021; 7: 134
        • Voorwerk L.
        • Slagter M.
        • Horlings H.M.
        • et al.
        Publisher Correction: Immune induction strategies in metastatic triple-negative breast cancer to enhance the sensitivity to PD-1 blockade: the TONIC trial.
        Nat Med. 2019; 25: 1175
        • Liu M.C.
        • Robinson P.A.
        • Yau C.
        • et al.
        Abstract P3-09-02: Evaluation of a novel agent plus standard neoadjuvant therapy in early stage, high-risk HER2 negative breast cancer: Results from the I-SPY 2 TRIAL.
        in: Poster session abstracts. American Association for Cancer Research, 2020https://doi.org/10.1158/1538-7445.sabcs19-p3-09-02
        • Sharma P.
        • Stecklein S.R.
        • Yoder R.
        • et al.
        Clinical and biomarker results of neoadjuvant phase II study of pembrolizumab and carboplatin plus docetaxel in triple-negative breast cancer (TNBC) (NeoPACT).
        J Clin Orthod. 2022; 40: 513
        • Loibl S.
        • Weber K.E.
        • Timms K.M.
        • et al.
        Survival analysis of carboplatin added to an anthracycline/taxane-based neoadjuvant chemotherapy and HRD score as predictor of response-final results from GeparSixto.
        Ann Oncol. 2018; 29: 2341-2347
        • Shepherd J.H.
        • Ballman K.
        • Polley M.Y.C.
        • et al.
        CALGB 40603 (alliance): Long-term outcomes and genomic correlates of response and survival after neoadjuvant chemotherapy with or without carboplatin and bevacizumab in triple-negative breast cancer.
        J Clin Oncol. 2022; 40: 1323-1334
        • Geyer C.E.
        • Sikov W.M.
        • Huober J.
        • et al.
        Long-term efficacy and safety of addition of carboplatin with or without veliparib to standard neoadjuvant chemotherapy in triple-negative breast cancer: 4-year follow-up data from BrighTNess, a randomized phase III trial.
        Ann Oncol. 2022; 33: 384-394
        • Nanda R.
        • Liu M.C.
        • Yau C.
        • 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; 6: 676-684
        • 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: 503
        • Masuda N.
        • Lee S.J.
        • Ohtani S.
        • et al.
        Adjuvant capecitabine for breast cancer after preoperative chemotherapy.
        N Engl J Med. 2017; 376: 2147-2159
        • Tutt A.N.J.
        • Garber J.
        • Gelber R.D.
        • et al.
        VP1-2022: Pre-specified event driven analysis of Overall Survival (OS) in the OlympiA phase III trial of adjuvant olaparib (OL) in germline BRCA1/2 mutation (gBRCAm) associated breast cancer.
        Ann Oncol. 2022; 33: 566-568
        • Vinayak S.
        • Tolaney S.M.
        • Schwartzberg L.S.
        • et al.
        TOPACIO/Keynote-162: Niraparib + pembrolizumab in patients (pts) with metastatic triple-negative breast cancer (TNBC), a phase 2 trial.
        J Clin Oncol. 2018; 36: 1011
        • Domchek S.M.
        • Postel-Vinay S.
        • Im S.A.
        • et al.
        Abstract OT3-05-03: MEDIOLA: An open-label, phase I/II basket study of olaparib (PARP inhibitor) and durvalumab (anti-PD-L1 antibody)–Additional breast cancer cohorts.
        in: Ongoing clinical trials. American Association for Cancer Research, 2019https://doi.org/10.1158/1538-7445.sabcs18-ot3-05-03
        • Denkert C.
        • von Minckwitz G.
        • Darb-Esfahani S.
        • et al.
        Tumour-infiltrating lymphocytes and prognosis in different subtypes of breast cancer: a pooled analysis of 3771 patients treated with neoadjuvant therapy.
        Lancet Oncol. 2018; 19: 40-50
        • de Jong V.M.T.
        • Wang Y.
        • Ter Hoeve N.D.
        • et al.
        Prognostic value of stromal tumor-infiltrating lymphocytes in young, node-negative, triple-negative breast cancer patients who did not receive (neo)adjuvant systemic therapy.
        J Clin Oncol. 2022; 40: 2361-2374
        • Karn T.
        • Denkert C.
        • Weber K.E.
        • et al.
        Tumor mutational burden and immune infiltration as independent predictors of response to neoadjuvant immune checkpoint inhibition in early TNBC in GeparNuevo.
        Ann Oncol. 2020; 31: 1216-1222
        • Bianchini G.
        • Huang C.S.
        • Egle D.
        • et al.
        LBA13 Tumour infiltrating lymphocytes (TILs), PD-L1 expression and their dynamics in the NeoTRIPaPDL1 trial.
        Ann Oncol. 2020; 31: S1145-S1146
        • Dugo M.
        • Huang C.S.
        • Egle D.
        • et al.
        Abstract P2-07-12: Triple negative breast cancer subtypes and early dynamics of the 27-gene IO score predict pCR in the NeoTRIPaPDL1 trial.
        Cancer Res. 2022; 82: 07-12
        • Sinn B.V.
        • Loibl S.
        • Karn T.
        • et al.
        Abstract PD5-05: Pre-therapeutic PD-L1 expression and dynamics of Ki-67 and gene expression during neoadjuvant immune-checkpoint blockade and chemotherapy to predict response within the GeparNuevo trial.
        in: Poster discussion abstracts. American Association for Cancer Research, 2019https://doi.org/10.1158/1538-7445.sabcs18-pd5-05
        • Winer E.P.
        • Lipatov O.
        • Im S.A.
        • et al.
        Pembrolizumab versus investigator-choice chemotherapy for metastatic triple-negative breast cancer (KEYNOTE-119): a randomised, open-label, phase 3 trial.
        Lancet Oncol. 2021; 22: 499-511
        • Tolaney S.M.
        • Kalinsky K.
        • Kaklamani V.G.
        • et al.
        Eribulin plus pembrolizumab in patients with metastatic triple-negative breast cancer (ENHANCE 1): A phase Ib/II study.
        Clin Cancer Res. 2021; 27: 3061-3068
        • Rugo H.S.
        • Schmid P.
        • Cescon D.W.
        • et al.
        Abstract GS3-01: Additional efficacy endpoints from the phase 3 KEYNOTE-355 study of pembrolizumab plus chemotherapy vs placebo plus chemotherapy as first-line therapy for locally recurrent inoperable or metastatic triple-negative breast cancer.
        in: General session abstracts. American Association for Cancer Research, 2021https://doi.org/10.1158/1538-7445.sabcs20-gs3-01
        • Schmid P.
        • Adams S.
        • Rugo H.S.
        • et al.
        Atezolizumab and nab-paclitaxel in advanced triple-negative breast cancer.
        N Engl J Med. 2018; 379: 2108-2121
        • Emens L.A.
        • Adams S.
        • Barrios C.H.
        • et al.
        First-line atezolizumab plus nab-paclitaxel for unresectable, locally advanced, or metastatic triple-negative breast cancer: IMpassion130 final overall survival analysis.
        Ann Oncol. 2021; 32: 983-993
        • Miles D.
        • Gligorov J.
        • André F.
        • et al.
        Primary results from IMpassion131, a double-blind, placebo-controlled, randomised phase III trial of first-line paclitaxel with or without atezolizumab for unresectable locally advanced/metastatic triple-negative breast cancer.
        Ann Oncol. 2021; 32: 994-1004
        • Wolchok J.D.
        • Rollin L.
        • Larkin J.
        Nivolumab and ipilimumab in advanced melanoma.
        N Engl J Med. 2017; 377: 2503-2504
        • Robert C.
        • Ribas A.
        • Schachter J.
        • et al.
        Pembrolizumab versus ipilimumab in advanced melanoma (KEYNOTE-006): post-hoc 5-year results from an open-label, multicentre, randomised, controlled, phase 3 study.
        Lancet Oncol. 2019; 20: 1239-1251
        • Gadgeel S.
        • Rodríguez-Abreu D.
        • Speranza G.
        • et al.
        Updated analysis from KEYNOTE-189: Pembrolizumab or placebo plus pemetrexed and platinum for previously untreated metastatic nonsquamous non-small-cell lung cancer.
        J Clin Oncol. 2020; 38: 1505-1517
        • Paz-Ares L.
        • Vicente D.
        • Tafreshi A.
        • et al.
        A randomized, placebo-controlled trial of pembrolizumab plus chemotherapy in patients with metastatic squamous NSCLC: Protocol-specified final analysis of KEYNOTE-407.
        J Thorac Oncol. 2020; 15: 1657-1669
        • Marron T.U.
        • Ryan A.E.
        • Reddy S.M.
        • et al.
        Considerations for treatment duration in responders to immune checkpoint inhibitors.
        J Immunother Cancer. 2021; 9: e001901
        • Bachelot T.
        • Filleron T.
        • Bieche I.
        • et al.
        Durvalumab compared to maintenance chemotherapy in metastatic breast cancer: the randomized phase II SAFIR02-BREAST IMMUNO trial.
        Nat Med. 2021; 27: 250-255
        • Rugo H.S.
        • Loi S.
        • Adams S.
        • et al.
        PD-L1 immunohistochemistry assay comparison in atezolizumab plus nab-paclitaxel-treated advanced triple-negative breast cancer.
        J Natl Cancer Inst. 2021; 113: 1733-1743
        • Rozenblit M.
        • Huang R.
        • Danziger N.
        • et al.
        Comparison of PD-L1 protein expression between primary tumors and metastatic lesions in triple negative breast cancers.
        J Immunother Cancer. 2020; 8: e001558
        • Emens L.A.
        • Molinero L.
        • Loi S.
        • et al.
        Atezolizumab and nab-paclitaxel in advanced triple-negative breast cancer: Biomarker evaluation of the IMpassion130 study.
        J Natl Cancer Inst. 2021; 113: 1005-1016
        • Barroso-Sousa R.
        • Keenan T.E.
        • Pernas S.
        • et al.
        Tumor mutational burden and PTEN alterations as molecular correlates of response to PD-1/L1 blockade in metastatic triple-negative breast cancer.
        Clin Cancer Res. 2020; 26: 2565-2572
        • Barroso-Sousa R.
        • Li T.
        • Reddy S.
        • et al.
        Abstract GS2-10: Nimbus: A phase 2 trial of nivolumab plus ipilimumab for patients with hypermutated her2-negative metastatic breast cancer (MBC).
        Cancer Res. 2022; 82 (GS2-10)
        • Alva A.S.
        • Mangat P.K.
        • Garrett-Mayer E.
        • et al.
        Pembrolizumab in patients with metastatic breast cancer with high tumor mutational burden: Results from the targeted agent and profiling utilization registry (TAPUR) study.
        J Clin Oncol. 2021; 39: 2443-2451
        • Haanen J.B.A.G.
        • Carbonnel F.
        • Robert C.
        • et al.
        Management of toxicities from immunotherapy: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up.
        Ann Oncol. 2018; 29: iv264-iv266
        • Magbanua M.J.M.
        • Swigart L.B.
        • Wu H.T.
        • et al.
        Circulating tumor DNA in neoadjuvant-treated breast cancer reflects response and survival.
        Ann Oncol. 2021; 32: 229-239
        • Isakoff S.J.
        • Adams S.
        • Soliman H.H.
        • et al.
        Abstract P3-09-15: A phase 1b study of PVX-410 (PVX) vaccine plus durvalumab (DUR) as adjuvant therapy in HLA-A2+ early stage triple negative breast cancer (eTNBC) to assess safety and immune response.
        in: Poster session abstracts. American Association for Cancer Research, 2020https://doi.org/10.1158/1538-7445.sabcs19-p3-09-15
        • Garrido-Castro A.C.
        • Keenan T.E.
        • Li T.
        • et al.
        Saci-IO HR+: Randomized phase II trial of sacituzumab govitecan (SG) +/- pembrolizumab in PD-L1+ hormone receptor-positive (HR+)/HER2- metastatic breast cancer (MBC).
        J Clin Oncol. 2021; 39: TPS1102
        • Garrido-Castro A.C.
        • Keenan T.E.
        • Li T.
        • et al.
        Saci-IO TNBC: Randomized phase II trial of sacituzumab govitecan (SG) +/- pembrolizumab in PD-L1– metastatic triple-negative breast cancer (mTNBC).
        J Clin Oncol. 2021; 39: TPS1106
        • Spring L.M.
        • Tolaney S.M.
        • Desai N.
        • et al.
        Abstract OT-03-06: Phase 2 study of response-guided neoadjuvant sacituzumab govitecan (IMMU-132) in patients with localized triple-negative breast cancer (NeoSTAR).
        in: Ongoing clinical trials abstracts. American Association for Cancer Research, 2021https://doi.org/10.1158/1538-7445.sabcs20-ot-03-06