Immunotherapy for Metastatic Breast Cancer

tibbionko-17-1-kapak

Berkan KARADURMUŞa , Nuri KARADURMUŞa
aUniversity of Health Sciences Gülhane Faculty of Medicine, Department of Medical Oncology, Ankara, Türkiye

Karadurmuş B, Karadurmuş N. Immunotherapy for metastatic breast cancer. In: Şendur MAN, ed. Current Immunotherapy Landscape for Solid Tumors. 1st ed. Ankara: Türkiye Klinikleri; 2024. p.58-64.

ABSTRACT
The appearance of immunotherapy, especially immune checkpoint inhibitors (ICIs), is a major revolution in the therapeutic management of solid tumor malignancies. Among breast cancer subgroups, the strongest evidence for ICI is in triple-negative breast cancer (TNBC). In TNBC patients, many preclinical studies have demonstrated enhanced anti-tumor immune responses with ICI treatment. The use of ICI as monotherapy or in combination with chemotherapy in patients with metastatic TNBC has been evaluated in clinical trials. Especially in first line, promising results have been obtained in patients whose tumors have high expression of programmed cell death 1 (PD-1) or programmed cell death ligand 1 (PD-L1). In the KEYNOTE-355 trial, Pembrolizumab combined with chemotherapy also improved progression-free survival and overall survival in metastatic TNBC patients with a PD-L1 combined positive score >10. Other sub-groups in which ICI trials are underway include hormone receptor-positive breast cancer and HER2-positive breast cancer. In these subgroups, ICI is being studied in combination with chemotherapy, targeted therapy and antibody-drug conjugates. A variety of new immunotherapeutic agents are being investigated across all subtypes, including new ICIs, cancer vaccines, adoptive cellular therapy, and oncolytic viruses.

Keywords: Immunotherapy; immune checkpoint inhibitors; breast neoplasms

Referanslar

  1. Sharpe AH, Pauken KE. The diverse functions of the PD1 inhibitory pathway. Nat Rev Immunol. 2018;18(3):153-67. [Crossref]  [PubMed]
  2. Gumusay O, Callan J, Rugo HS. Immunotherapy toxicity: identification and management. Breast Cancer Res Treat. 2022;192(1):1-17. [Crossref]  [PubMed]  [PMC]
  3. Naidoo J, Page DB, Li BT, Connell LC, Schindler K, Lacouture ME, et al. Toxicities of the anti-PD-1 and anti-PD-L1 immune checkpoint antibodies. Ann Oncol. 2015;26(12):2375-91. Erratum in: Ann Oncol. 2016;27(7):1362. [Crossref]  [PubMed]  [PMC]
  4. Martins F, Sofiya L, Sykiotis GP, Lamine F, Maillard M, Fraga M, et al. Adverse effects of immune-checkpoint inhibitors: epidemiology, management and surveillance. Nat Rev Clin Oncol. 2019;16(9):563-80. [Crossref]  [PubMed]
  5. Unger JM, Vaidya R, Albain KS, LeBlanc M, Minasian LM, Gotay CC, et al. Sex Differences in Risk of Severe Adverse Events in Patients Receiving Immunotherapy, Targeted Therapy, or Chemotherapy in Cancer Clinical Trials. J Clin Oncol. 2022;40(13):1474-86. [Crossref]  [PubMed]  [PMC]
  6. Maher VE, Fernandes LL, Weinstock C, Tang S, Agarwal S, Brave M, et al. Analysis of the Association Between Adverse Events and Outcome in Patients Receiving a Programmed Death Protein 1 or Programmed Death Ligand 1 Antibody. J Clin Oncol. 2019;37(30):2730-7. [Crossref]  [PubMed]
  7. Schneider BJ, Naidoo J, Santomasso BD, Lacchetti C, Adkins S, Anadkat M, et al. Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: ASCO Guideline Update. J Clin Oncol. 2021;39(36):4073-126. Erratum in: J Clin Oncol. 2022;40(3):315. [Crossref]  [PubMed]
  8. Rugo HS, Loi S, Adams S, Schmid P, Schneeweiss A, Barrios CH, et al. Performance of PD-L1 immunohistochemistry (IHC) assays in unresectable locally advanced or metastatic triple-negative breast cancer (mTNBC): Post-hoc analysis of IMpassion130. Ann Oncol 2019;30:v858-v859. [Crossref]
  9. Gatti-Mays ME, Balko JM, Gameiro SR, Bear HD, Prabhakaran S, Fukui J, et al. If we build it they will come: targeting the immune response to breast cancer. NPJ Breast Cancer. 2019;5:37. [Crossref]  [PubMed]  [PMC]
  10. Stanton SE, Adams S, Disis ML. Variation in the Incidence and Magnitude of Tumor-Infiltrating Lymphocytes in Breast Cancer Subtypes: A Systematic Review. JAMA Oncol. 2016;2(10):1354-60. [Crossref]  [PubMed]
  11. Nanda R, Chow LQ, Dees EC, Berger R, Gupta S, Geva R, et al. Pembrolizumab in Patients With Advanced Triple-Negative Breast Cancer: Phase Ib KEYNOTE-012 Study. J Clin Oncol. 2016;34(21):2460-7. [Crossref]  [PubMed]  [PMC]
  12. Adams S, Schmid P, Rugo HS, Winer EP, Loirat D, Awada A, 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(3):397-404. [Crossref]  [PubMed]
  13. Adams S, Loi S, Toppmeyer D, Cescon DW, De Laurentiis M, Nanda R, et al. Pembrolizumab monotherapy for previously untreated, PD-L1-positive, metastatic triple-negative breast cancer: cohort B of the phase II KEYNOTE-086 study. Ann Oncol. 2019;30(3):405-11. [Crossref]  [PubMed]
  14. Emens LA, Cruz C, Eder JP, Braiteh F, Chung C, Tolaney SM, 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(1):74-82. [Crossref]  [PubMed]  [PMC]
  15. Dirix LY, Takacs I, Jerusalem G, Nikolinakos P, Arkenau HT, Forero-Torres A, 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(3):671-86. [Crossref]  [PubMed]  [PMC]
  16. Winer EP, Lipatov O, Im SA, Goncalves A, Muñoz-Couselo E, Lee KS, et al.; KEYNOTE-119 investigators. Pembrolizumab versus investigator-choice chemotherapy for metastatic triple-negative breast cancer (KEYNOTE-119): a randomised, open-label, phase 3 trial. Lancet Oncol. 2021;22(4):499-511. [Crossref]  [PubMed]
  17. Loi S, Winer E, Lipatov O, Goncalves A. Abstract PD5-03: Relationship between tumor-infiltrating lymphocytes (TILs) and outcomes in the KEYNOTE-119 study of pembrolizumab vs chemotherapy for previously treated metastatic triple-negative breast cancer (mTNBC). Cancer research 2020;80(4):1158-9. [Crossref]
  18. Senovilla L, Vitale I, Martins I, Tailler M, Pailleret C, Michaud M, et al. An immunosurveillance mechanism controls cancer cell ploidy. Science. 2012;337(6102):1678-84. [Crossref]  [PubMed]
  19. Schmid P, Adams S, Rugo HS, Schneeweiss A, Barrios CH, Iwata H, et al.; IMpassion130 Trial Investigators. Atezolizumab and Nab-Paclitaxel in Advanced Triple-Negative Breast Cancer. N Engl J Med. 2018;379(22):2108-21. [Crossref]  [PubMed]
  20. Emens LA, Adams S, Barrios CH, Diéras V, Iwata H, Loi S, 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(8):983-93. Erratum in: Ann Oncol. 2021;32(12):1650. [Crossref]  [PubMed]
  21. Miles D, Gligorov J, André F, Cameron D, Schneeweiss A, Barrios C, et al.; IMpassion131 investigators. 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(8):994-1004. [Crossref]  [PubMed]
  22. Franzoi MA, de Azambuja E. Atezolizumab in metastatic triple-negative breast cancer: IMpassion130 and 131 trials - how to explain different results? ESMO Open. 2020;5(6):e001112. [Crossref]  [PubMed]  [PMC]
  23. Untch M, Jackisch C, Schneeweiss A, Conrad B, Aktas B, Denkert C, et al.; German Breast Group (GBG); Arbeitsgemeinschaft Gynäkologische Onkologie-Breast (AGO-B) Investigators. Nab-paclitaxel versus solvent-based paclitaxel in neoadjuvant chemotherapy for early breast cancer (GeparSepto-GBG 69): a randomised, phase 3 trial. Lancet Oncol. 2016;17(3):345-56. Erratum in: Lancet Oncol. 2016;17 (7):e270. [Crossref]  [PubMed]
  24. Cortes J, Rugo HS, Cescon DW, Im SA, Yusof MM, Gallardo C, et al.; KEYNOTE-355 Investigators. Pembrolizumab plus Chemotherapy in Advanced Triple-Negative Breast Cancer. N Engl J Med. 2022;387(3):217-26. [Crossref]  [PubMed]
  25. Rugo H, Schmid P, Cescon D, Nowecki Z, Im S, Yusof M. 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. San Antonio breast cancer symposium. Cancer Res. 2021:81(4_Supplement):GS3-01. [Crossref]
  26. Cortés Castán J, Cescon DW, Rugo HS, Im SA, Yuso M, Gallardo C, Lipatov O, et al. KEYNOTE-355: Final results from a randomized, doubleblind phase III study of first-line pembrolizumab+ chemotherapy vs placebo+ chemotherapy for metastatic TNBC. Ann Oncol. 2021;32(suppl_5):S1283-S46. [Crossref]
  27. Tolaney SM, Kalinsky K, Kaklamani VG, D'Adamo DR, Aktan G, Tsai ML, 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(11):3061-8. [Crossref]  [PubMed]
  28. Voorwerk L, Slagter M, Horlings HM, Sikorska K, van de Vijver KK, de Maaker M, et al. Immune induction strategies in metastatic triple-negative breast cancer to enhance the sensitivity to PD-1 blockade: the TONIC trial. Nat Med. 2019;25(6):920-8. Erratum in: Nat Med. 2019. [Crossref]  [PubMed]
  29. Modi S, Jacot W, Yamashita T, Sohn J, Vidal M, Tokunaga E, et al.; DESTINY-Breast04 Trial Investigators. Trastuzumab Deruxtecan in Previously Treated HER2-Low Advanced Breast Cancer. N Engl J Med. 2022;387(1):9-20. [Crossref]  [PubMed]  [PMC]
  30. Saini KS, Punie K, Twelves C, Bortini S, de Azambuja E, Anderson S, et al. Antibody-drug conjugates, immune-checkpoint inhibitors, and their combination in breast cancer therapeutics. Expert Opin Biol Ther. 2021;21(7):945-62. [Crossref]  [PubMed]
  31. Galluzzi L, Humeau J, Buqué A, Zitvogel L, Kroemer G. Immunostimulation with chemotherapy in the era of immune checkpoint inhibitors. Nat Rev Clin Oncol. 2020;17(12):725-41. [Crossref]  [PubMed]
  32. Garrido-Castro AC, Keenan TE, Li T, Lange P, Callahan C, Guerriero J, 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(15_suppl). [Crossref]
  33. Boni V, Alemany C, Meisel J, Sinha R, Sterrenberg D, Tkaczuk KHR, et al. SGNLVA-002: Single arm, open label, phase Ib/II study of ladiratuzumab vedotin (LV) in combination with pembrolizumab for first-line treatment of patients with unresectable locally-advanced or metastatic triple-negative breast cancer. Ann Oncol. J Clin Oncol. 2019;37(15_suppl). [Crossref]
  34. Jiao S, Xia W, Yamaguchi H, Wei Y, Chen MK, Hsu JM, et al. PARP Inhibitor Upregulates PD-L1 Expression and Enhances Cancer-Associated Immunosuppression. Clin Cancer Res. 2017;23(14):3711-20. [Crossref]  [PubMed]  [PMC]
  35. Domchek SM, Postel-Vinay S, Im SA, Park YH, Delord JP, Italiano A, Aet al. Olaparib and durvalumab in patients with germline BRCA-mutated metastatic breast cancer (MEDIOLA): an open-label, multicentre, phase 1/2, basket study. Lancet Oncol. 2020;21(9):1155-64. [Crossref]  [PubMed]
  36. Vinayak S, Tolaney SM, Schwartzberg L, Mita M, McCann G, Tan AR, et al. Open-label Clinical Trial of Niraparib Combined With Pembrolizumab for Treatment of Advanced or Metastatic Triple-Negative Breast Cancer. JAMA Oncol. 2019;5(8):1132-40. [Crossref]  [PubMed]  [PMC]
  37. Adams S, Othus M, Patel SP, Miller KD, Chugh R, Schuetze SM, et al. A Multicenter Phase II Trial of Ipilimumab and Nivolumab in Unresectable or Metastatic Metaplastic Breast Cancer: Cohort 36 of Dual Anti-CTLA-4 and Anti-PD-1 Blockade in Rare Tumors (DART, SWOG S1609). Clin Cancer Res. 2022;28(2):271-8. [Crossref]  [PubMed]  [PMC]
  38. Alva AS, Mangat PK, Garrett-Mayer E, Halabi S, Hansra D, Calfa CJ, 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(22):2443-51. [Crossref]  [PubMed]
  39. Barroso-Sousa R, Li T, Reddy S, Emens LA, Overmoyer B, Lange P, 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 Research 2022;82(4_Supple):GS2-10. [Crossref]
  40. Litchfield K, Reading JL, Puttick C, Thakkar K, Abbosh C, Bentham R, et al. Meta-analysis of tumor- and T cell-intrinsic mechanisms of sensitization to checkpoint inhibition. Cell. 2021;184(3):596-614.e14. [Crossref]  [PubMed]  [PMC]
  41. Takahashi M, Cortés J, Dent R, Pusztai L, McArthur H, Kümmel S, et al. Pembrolizumab Plus Chemotherapy Followed by Pembrolizumab in Patients With Early Triple-Negative Breast Cancer: A Secondary Analysis of a Randomized Clinical Trial. JAMA Netw Open. 2023;6(11):e2342107. [Crossref]  [PubMed]  [PMC]
  42. Mittendorf EA, Zhang H, Barrios CH, Saji S, Jung KH, Hegg R, 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(10257):1090-100. [Crossref]  [PubMed]
  43. Yee D, Shatsky RA, Yau C, Wolf DM, Nanda E, van't Veer L, et al. Improved pathologic complete response rates for triple-negative breast cancer in the I-SPY2 Trial. J Clin Oncol. 2022;40(16_suppl). [Crossref]
  44. Garcia-Diaz A, Shin DS, Moreno BH, Saco J, Escuin-Ordinas H, Rodriguez GA, et al. Interferon Receptor Signaling Pathways Regulating PD-L1 and PD-L2 Expression. Cell Rep. 2017;19(6):1189-1201. Erratum in: Cell Rep. 2019;29(11):3766. [Crossref]  [PubMed]  [PMC]
  45. Corti C, Nicolò E, Curigliano G. Novel immune targets for the treatment of triple-negative breast cancer. Expert Opin Ther Targets. 2021;25(10):815-34. [Crossref]  [PubMed]
  46. CAR T. Cells: Engineering immune cells to treat cancer-NCI. 2013. [Link]
  47. Geng P, Chi Y, Yuan Y, Yang M, Zhao X, Liu Z, et al. Novel chimeric antigen receptor T cell-based immunotherapy: a perspective for triple-negative breast cancer. Front Cell Dev Biol. 2023;11:1158539. [Crossref]  [PubMed]  [PMC]
  48. Andtbacka RH, Kaufman HL, Collichio F, Amatruda T, Senzer N, Chesney J, et al. Talimogene Laherparepvec Improves Durable Response Rate in Patients With Advanced Melanoma. J Clin Oncol. 2015;33(25):2780-8. [Crossref]  [PubMed]
  49. Karn T, Denkert C, Weber KE, Holtrich U, Hanusch C, Sinn BV, 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(9):1216-22. [Crossref]  [PubMed]
  50. Loi S, Giobbie-Hurder A, Gombos A, Bachelot T, Hui R, Curigliano G, et al.; International Breast Cancer Study Group and the Breast International Group. Pembrolizumab plus trastuzumab in trastuzumab-resistant, advanced, HER2-positive breast cancer (PANACEA): a single-arm, multicentre, phase 1b-2 trial. Lancet Oncol. 2019;20(3):371-82. [Crossref]  [PubMed]
  51. Ahn HK, Sim SH, Suh KJ, Kim MH, Jeong JH, Kim JY, et al. Response Rate and Safety of a Neoadjuvant Pertuzumab, Atezolizumab, Docetaxel, and Trastuzumab Regimen for Patients With ERBB2-Positive Stage II/III Breast Cancer: The Neo-PATH Phase 2 Nonrandomized Clinical Trial. JAMA Oncol. 2022;8(9):1271-7. [Crossref]  [PubMed]  [PMC]
  52. Rugo HS, Delord JP, Im SA, Ott PA, Piha-Paul SA, Bedard PL, et al. Safety and Antitumor Activity of Pembrolizumab in Patients with Estrogen Receptor-Positive/Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer. Clin Cancer Res. 2018;24(12):2804-11. [Crossref]  [PubMed]