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Review

Immune checkpoint inhibition in early-stage triple-negative breast cancer

, , &
Pages 1225-1238 | Received 17 Jan 2022, Accepted 19 Oct 2022, Published online: 14 Nov 2022

References

  • Pardoll DM, Topalian SL. The role of CD4+ T cell responses in antitumor immunity. Curr Opin Immunol. 1998 Oct 1; 10(5):588–594.
  • Antonia SJ, Villegas A, Daniel D, et al. Durvalumab after chemoradiotherapy in stage III non–small-cell lung cancer. N Engl J Med. 2017 Nov 16 377(20):1919–1929.
  • Gandhi L, Rodríguez-Abreu D, Gadgeel S, et al. Pembrolizumab plus chemotherapy in metastatic non–small-cell lung cancer. N Engl J Med. 2018 May 31 378(22):2078–2092.
  • Hodi FS, Chiarion-Sileni V, Gonzalez R, et al. Nivolumab plus ipilimumab or nivolumab alone versus ipilimumab alone in advanced melanoma (CheckMate 067): 4-year outcomes of a multicentre, randomised, phase 3 trial. Lancet Oncol. 2018 Nov 1 19(11):1480–1492.
  • Rini BI, Plimack ER, Stus V, et al. Pembrolizumab plus axitinib versus sunitinib for advanced renal-cell carcinoma. N Engl J Med. 2019 Mar 21 380(12):1116–1127.
  • Schmid P, Cortes J, Pusztai L, et al. Pembrolizumab for early triple-negative breast cancer. N Engl J Med. 2020 Feb 27;382(9):810–821.
  • Mittendorf EA, Philips AV, Meric-Bernstam F, et al. PD-L1 expression in triple-negative breast cancer. Cancer Immunology Research. 2014 Apr 1 2(4):361–370.
  • Denkert C, Loibl S, Noske A, et al. Tumor-associated lymphocytes as an independent predictor of response to neoadjuvant chemotherapy in breast cancer. J Clin Oncol. 2010 Jan 1 28(1):105–113.
  • Ruffell B, Au A, Rugo HS, et al. Leukocyte composition of human breast cancer. Proceedings of the National Academy of Sciences, USA. 2012 Feb 21;109( 8):2796–2801.
  • Coventry BJ, Weightman MJ, Bradley J, et al. Immune profiling in human breast cancer using high-sensitivity detection and analysis techniques. JRSM Open. 2015 Sep 22;6(9):2054270415603909. PMID: 26464809; PMCID: PMC4589078.
  • Havel JJ, Chowell D, Chan TA. The evolving landscape of biomarkers for checkpoint inhibitor immunotherapy. Nat Rev Cancer. 2019 Mar;19(3):133–150.
  • Mao Y, Qu Q, Chen X, et al. The prognostic value of tumor-infiltrating lymphocytes in breast cancer: a systematic review and meta-analysis. PloS one. 2016 Apr 13 11(4):e0152500.
  • 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 Mar 1 37(7):559.
  • Adams S, Gray RJ, Demaria S, et al. Prognostic value of tumor-infiltrating lymphocytes in triple-negative breast cancers from two phase III randomized adjuvant breast cancer trials: ECOG 2197 and ECOG 1199. J Clin Oncol. 2014 Sep 20 32(27):2959.
  • Kim JY, Kronbichler A, Eisenhut M, et al. Tumor mutational burden and efficacy of immune checkpoint inhibitors: a systematic review and meta-analysis. Cancers (Basel). 2019 Nov;11(11):1798.
  • Thomas A, Routh ED, Pullikuth A, et al. Tumor mutational burden is a determinant of immune-mediated survival in breast cancer. Oncoimmunology. 2018 Oct 3 7(10):e1490854.
  • Karn T, Denkert C, Weber KE, 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 Sep 1 31(9):1216–1222.
  • 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 Aug 1 30(8):1279–1288.
  • Schmid P, Rugo HS, Adams S, et al. Atezolizumab plus nab-paclitaxel as first-line treatment for unresectable, locally advanced or metastatic triple-negative breast cancer (IMpassion130): updated efficacy results from a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2020 Jan 1 21(1):44–59.
  • Vennapusa B, Baker B, Kowanetz M, et al. Development of a PD-L1 complementary diagnostic immunohistochemistry assay (SP142) for atezolizumab. Appl Immunohistochem Mol Morphol. 2019 Feb;27(2):92.
  • Nanda R, Chow LQ, Dees EC, et al. pembrolizumab in patients with advanced triple-negative breast cancer: phase Ib KEYNOTE-012 study. J Clin Oncol. 2016 Jul 20 34(21):2460–2467.
  • Adams S, Schmid P, Rugo HS, et al. Pembrolizumab monotherapy for previously treated metastatic triple-negative breast cancer: cohort A of the phase II KEYNOTE-086 study. Annals of Oncology. 2019 Mar 1 30(3):397–404.
  • Winer EP, Lipatov O, Im SA, 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 Apr;22(4):499–511.
  • Emens LA, Cruz C, Eder JP, 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 Jan 1 5(1):74–82.
  • Cortes J, Cescon DW, Rugo HS, 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 Dec 5 396(10265):1817–1828.
  • 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 Aug 1 32(8):994–1004.
  • Santa-Maria CA, Kato T, Park JH, et al. A pilot study of durvalumab and tremelimumab and immunogenomic dynamics in metastatic breast cancer. Oncotarget. 2018 Apr 10 9(27):18985–18996.
  • National Library of Medicine (U.S). Testing the addition of an individualized vaccine to nab-paclitaxel, durvalumab and tremelimumab and chemotherapy in patients with metastatic triple negative breast cancer. [Internet]. 2018. Available from: https://clinicaltrials.gov/ct2/show/NCT03606967?term=ipilimumab&cond=Breast+Cancer&draw=2&rank=30.
  • Barroso-Sousa R, Li T, Reddy S, et al. Nimbus: a phase 2 trial of nivolumab plus ipilimumab for patients with hypermutated her2-negative metastatic breast cancer (MBC). Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. AACR; Cancer Res 2022;82( 4): Abstract nr GS2-10.
  • European Medicines Agency. Draft guideline on the role of the pathological complete response as an endpoint in neoadjuvant breast cancer studies [Internet].2014; [cited2022 8]. Available from: http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2014/04/WC500165781.pdf.
  • Burstein HJ, Curigliano G, Loibl S, et al. Estimating the benefits of therapy for early-stage breast cancer: the St. gallen international consensus guidelines for the primary therapy of early breast cancer 2019. Annals of Oncology. 2019 Oct 1 30(10):1541–1557.
  • Sikov WM, Berry DA, Perou CM, et al. Impact of the addition of carboplatin and/or bevacizumab to neoadjuvant once-per-week paclitaxel followed by dose-dense doxorubicin and cyclophosphamide on pathologic complete response rates in stage II to III triple-negative breast cancer: CALGB 40603 Alliance. J Clin Oncol. 2015 Jan 1;33(1):13.
  • Schmid P, Salgado R, Park YH, et al. 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. Annals of Oncology. 2020 May;31(5):569–581.
  • Nanda R, Liu MC, 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 May 1;6(5):676–684.
  • Liu MC, Robinson PA, Yau C, et al. 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 [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80( 4):9.
  • Von Minckwitz G, Schneeweiss A, Loibl S, et al. Neoadjuvant carboplatin in patients with triple-negative and HER2-positive early breast cancer (GeparSixto; GBG 66): a randomised phase 2 trial. Lancet Oncol. 2014 Jun 1 15(7):747–756.
  • Schmid P, Cortes J, Dent R, et al. KEYNOTE-522: phase 3 study of neoadjuvant pembrolizumab plus chemotherapy versus placebo plus chemotherapy, followed by adjuvant pembrolizumab versus placebo for early-stage triple-negative breast cancer. Ann Oncol 2021 32(9):1198–1200.
  • Yang H, Shen K, Zhu C, et al. Safety and efficacy of durvalumab (MEDI4736) in various solid tumors. [Cdata[drug Design, Development and Therapy]. 2018;12:2085.
  • Denkert C, Wienert S, Poterie A, et al. Standardized evaluation of tumor-infiltrating lymphocytes in breast cancer: results of the ring studies of the international immuno-oncology biomarker working group. Modern Pathology. 2016 Oct;29(10):1155–1164.
  • Untch M, Jackisch C, Schneeweiss A, et al. Nab-paclitaxel versus solvent-based paclitaxel in neoadjuvant chemotherapy for early breast cancer (GeparSepto—GBG 69): a randomised, phase 3 trial. Lancet Oncol. 2016 Mar 1 17(3):345–356.
  • Mittendorf EA, Zhang H, Barrios CH, 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 Oct 10 396(10257):1090–1100.
  • Gianni L, Huang C-S, Egle D, 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. Cancer Res 2020. 80(3): GS3–04.
  • Geyer CE, Loibl S, Rastogi P, et al. NSABP B-59/GBG 96-GeparDouze: a randomized double-blind phase III clinical trial of neoadjuvant chemotherapy (NAC) with atezolizumab or placebo in Patients (pts) with triple negative breast cancer (TNBC) followed by adjuvant atezolizumab or placebo. Journal of Clinical Oncology. 2019 May 26;36(15_suppl): TPS603–TPS603.
  • National Library of Medicine (U.S.). Clinical trial of neoadjuvant chemotherapy with atezolizumab or placebo in patients with triple-negative breast cancer followed after surgery by atezolizumab or placebo. [Internet]. 2017; [cited 2022 August]. Available from: https://clinicaltrials.gov/ct2/show/NCT03281954.
  • Comen EA, Bryce Y, Page DB, et al. Preoperative checkpoint inhibition (CPI) and cryoablation (Cryo) in women with early-stage breast cancer (ESBC). Journal of Clinical Oncology. 2019;37(15_suppl):592.
  • National Library of Medicine (U.S). Peri-Operative ipilimumab+nivolumab and cryoablation in women with triple-negative breast cancer. [Internet]. 2022; [cited 2022 August]. Available from: https://clinicaltrials.gov/ct2/show/NCT03546686.
  • Postow MA, Sidlow R, Hellmann MD. Immune-related adverse events associated with immune checkpoint blockade. New England Journal of Medicine. 2018 Jan 11; 378(2):1216–1222.
  • Andreopoulou E, Sparano JA. Chemotherapy in patients with anthracycline and taxane-pretreated metastatic breast cancer: an overview. Current Breast Cancer Reports. 2013 Mar 1; 5(1):42–50.
  • JM Y. Clinical features, predictive correlates, and pathophysiology of immune-related adverse events in immune checkpoint inhibitor treatments in cancer: a short review. ImmunoTargets Ther. 2017;6(73).
  • Barroso-Sousa R, Barry WT, Garrido-Castro AC, et al. Incidence of endocrine dysfunction following the use of different immune checkpoint inhibitor regimens: a systematic review and meta-analysis. JAMA Oncol. 2018 Feb 1 4(2):173–182.
  • Baxi S, Yang A, Gennarelli RL, et al.Immune-related adverse events for anti-PD-1 and anti-PD-L1 drugs: systematic review and meta-analysis.Br Med J. 2018 Mar 14;360:k793.
  • Abid H, Khavandi M, Siddiqui N, et al. Incidence and Risk of Thyroid Dysfunction in Advanced or Metastatic Non-small Cell Lung Cancer Patients Treated with Pembrolizumab: a Meta-analysis. Cureus. 2019 Oct;11(10):e5997.
  • D’Abreo N, Adams S. Immune-checkpoint inhibition for metastatic triple-negative breast cancer: safety first? Nature Reviews Clinical Oncology. 2019 Jul;16(7):399–400.
  • Weber JS, Hodi FS, Wolchok JD, et al. Safety profile of nivolumab monotherapy: a pooled analysis of patients with advanced melanoma. Journal of Clinical Oncology. 2017 Mar;35(7):785–792.
  • Horvat TZ, Adel NG, Dang T, et al. Immune-related adverse events, need for systemic immunosuppression, and effects on survival and time to treatment failure in patients with melanoma treated with ipilimumab at memorial sloan kettering cancer center. Journal of Clinical Oncology. 2015 Oct 1 33(28):3193–3198.
  • Garutti M, Lambertini M, Puglisi F. Checkpoint inhibitors, fertility, pregnancy, and sexual life: a systematic review. ESMO open. 2021 Oct 1; 6(5):100276.
  • Brahmer JR, Lacchetti C, Schneider BJ, et al. Management of immune-related adverse events in patients treated with immune checkpoint inhibitor therapy: American society of clinical oncology clinical practice guideline. Journal of Clinical Oncology. 2018 Jun 10 36(17):1714–1768.
  • Emens LA, Adams S, Cimino-Mathews A, et al. Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immunotherapy for the treatment of breast cancer. Journal for ImmunoTherapy of Cancer. 2021;9(8):e002597.
  • Cretella C, Digiacomo D, Giovannetti G, et al. PTEN alterations as a potential mechanism for tumor cell escape from PD-1/PD-L1 inhibition. Cancers (Basel). 2019 Sep;11(9):1318.
  • Schmid P, Bofill FJS, Bermejo B, et al. 123MO BARBICAN: a randomized, phase II study to determine the contribution of ipatasertib to neoadjuvant chemotherapy plus atezolizumab in women with triple-negative breast cancer. Annals of Oncology. 2021 Sep 1;32:S411–2.
  • Jiao S, Xia W, Yamaguchi H, et al. PARP inhibitor upregulates PD-L1 expression and enhances cancer-associated immunosuppression. Clinical Cancer Research. 2017 Jul 15 23(14):3711–3720.
  • Vikas P, Borcherding N, Chennamadhavuni A, et al. Therapeutic potential of combining PARP inhibitor and immunotherapy in solid tumors. Frontiers in Oncology. 2020 Apr 28;10:570.
  • Vinayak S, Tolaney SM, Schwartzberg LS, et al. TOPACIO/Keynote-162: niraparib + pembrolizumab in patients (pts) with metastatic triple-negative breast cancer (TNBC), a phase 2 trial. Journal of Clinical Oncology. 2018 May;36(15_suppl):1011.
  • National Library of Medicine (U.S). Radiation, Immunotherapy and PARP inhibitor in triple negative breast cancer (NADiR). [Internet]. 2021; [cited 2022 August]. Available from: https://clinicaltrials.gov/ct2/show/NCT04837209.
  • Pusztai L, Yau C, Wolf DM, et al. Durvalumab with olaparib and paclitaxel for high-risk HER2-negative stage II/III breast cancer: results from the adaptively randomized I-SPY2 trial. Cancer Cell. 2021 Jul 12 39(7):989–998.e5.
  • Pusztai L, Barlow WE, Ganz PA, et al. SWOG S1418/NRG -BR006: a randomized, phase III trial to evaluate the efficacy and safety of MK-3475 as adjuvant therapy for triple receptor-negative breast cancer with > 1 cm residual invasive cancer or positive lymph nodes (>pN1mic) after neoadjuvant chemotherapy. Proceedings of the 2017 San Antonio Breast Cancer Symposium, San Antonio, Texas; 2017 Dec 5-9; AACR; Cancer Res 2018;78( 4): 4.
  • National Library of Medicine (U.S). a study comparing atezolizumab (anti pd-l1 antibody) in combination with adjuvant anthracycline/taxane-based chemotherapy versus chemotherapy alone in patients with operable triple-negative breast cancer (IMpassion030). [Internet]. 2018; [cited 2022 August]. Available from: https://clinicaltrials.gov/ct2/show/NCT03498716.
  • National Library of Medicine (U.S). Pre-operative trial for breast cancer with nivolumab in combination with novel IO (BELLINI). [Internet]. 2019; [cited 2022 August]. Available from: https://clinicaltrials.gov/ct2/show/NCT03815890?term=ipilimumab&cond=Breast+Cancer&draw=2&rank=12.
  • National Library of Medicine (U.S). Evaluate the clinical benefit of a post-operative treatment associating radiotherapy + nivolumab + ipilimumab versus radiotherapy + capecitabine for triple negative breast cancer patients with residual disease (BreastImmune03). [Internet]. 2019; [cited 2022 August]. Available from: https://clinicaltrials.gov/ct2/show/NCT03818685.
  • Conte PF, Dieci MV, Bisagni G, et al. Phase III randomized study of adjuvant treatment with the ANTI-PD-L1 antibody avelumab for high-risk triple negative breast cancer patients: the A-BRAVE trial. J ClinOncol. 2020 May 25 38(15_suppl): TPS598- TPS598.
  • National Library of Medicine (U.S). Adjuvant treatment for high-risk triple negative breast cancer patients with the anti-PD-l1 antibody avelumab (A-Brave). [Internet]. 2016; [cited 2022 August]. Available from: https://clinicaltrials.gov/ct2/show/NCT02926196.
  • National Library of Medicine (U.S.). An open-label phase II trial evaluating the efficacy and safety of sintilimab plus anlotinib combined with chemotherapy as neoadjuvant therapy in early-stage triple-negative breast cancer (NeoSACT) [Internet]. 2021; [cited 2022 August]. Available from: https://clinicaltrials.gov/ct2/history/NCT04877821.
  • The I-SPY trials agent information cemiplimab + REGN3767. [Internet]. 2020 [cited 2022 8]. Available from: https://www.ispytrials.org/agents/regn3767
  • The I-SPY Trials. Recent results & agents. [Internet]. 2022; [cited 2022 August]. Available from: https://www.ispytrials.org/results/past-agents.
  • Masuda N, Lee S-J, Ohtani S, et al. Adjuvant capecitabine for breast cancer after preoperative chemotherapy. N Engl J Med. 2017 Jun 1;376(22):2147–2159.
  • Tutt ANJ, Garber JE, Kaufman B, et al. Adjuvant olaparib for patients with BRCA1 - or BRCA2 -Mutated breast cancer. N EnglJMed. 2021 Jun 24;384(25):2394–2405.

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