Neratinib as adjuvant therapy in patients with HER2 positive breast cancer: expert opinion

Papers of special note have been highlighted as: • of interest

References

• 1. Sung H, Ferlay J, Siegel RL et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA. Cancer J. Clin. 71, 209–249 (2021).
  MedlineGoogle Scholar
• 2. World Health Organization (WHO). Breast Cancer (2021). www.who.int/news-room/fact-sheets/detail/breast-cancer (Accessed 16 June 2023).
  Google Scholar
• 3. Fragomeni SM, Sciallis A, Jeruss JS. Molecular subtypes and local-regional control of breast cancer. Surg. Oncol. Clin. N. Am. 27, 95–120 (2018).
  MedlineGoogle Scholar
• 4. Harbeck N, Penault-Llorca F, Cortes J et al. Breast cancer. Nat. Rev. Dis. Primers. 5, 66 (2019). • This review provides an in-depth summary of breast cancer epidemiology, pathogenesis, diagnosis and management.
  MedlineGoogle Scholar
• 5. Chilà G, Guarini V, Galizia D et al. The clinical efficacy and safety of neratinib in combination with capecitabine for the treatment of adult patients with advanced or metastatic HER2-positive breast cancer. Drug Des. Devel. Ther. 15, 2711–2720 (2021). • This review discusses the clinical efficacy and safety of neratinib + capecitabine in advanced/metastatic HER2-positive breast cancer; the treatment combination has improved progression-free survival, response duration and time to intervention compared with lapatinib + capecitabine.
  MedlineGoogle Scholar
• 6. Slamon D, Eiermann W, Robert N et al. Adjuvant trastuzumab in HER2-positive breast cancer. N. Engl. J. Med. 365, 1273–1283 (2011).
  Medline CASGoogle Scholar
• 7. McGee SF, Clemons M, Savard MF. Evolving role of risk tailored therapy in early stage HER2-positive breast cancer: a Canadian perspective. Curr. Oncol. 29, 4125–4137 (2022). • This review summarizes data supporting risk tailored therapy in early stage HER2-positive breast cancer from key Canadian and international risk tailored trials.
  MedlineGoogle Scholar
• 8. Albanell J, Baselga J. Trastuzumab, a humanized anti-HER2 monoclonal antibody, for the treatment of breast cancer. Drugs Today (Barc.). 35, 931–946 (1999).
  Medline CASGoogle Scholar
• 9. EMA. Herceptin 150 mg powder for concentrate for solution for infusion (2000). www.ema.europa.eu/en/documents/product-information/herceptin-epar-product-information_en.pdf (Accessed 16 June 2023).
  Google Scholar
• 10. Yu S, Liu Q, Han X et al. Development and clinical application of anti-HER2 monoclonal and bispecific antibodies for cancer treatment. Exp. Hematol. Oncol. 6, 31 (2017).
  MedlineGoogle Scholar
• 11. Lambertini M, Pondé NF, Solinas C, de Azambuja E. Adjuvant trastuzumab: a 10-year overview of its benefit. Expert Rev. Anticancer Ther. 17, 61–74 (2017).
  Medline CASGoogle Scholar
• 12. US FDA. NERLYNX^® (neratinib) tablets, for oral use (2017). www.accessdata.fda.gov/drugsatfda_docs/label/2020/208051s005s006lbl.pdf (Accessed 16 June 2023).
  Google Scholar
• 13. Burstein HJ, Sun Y, Dirix LY et al. Neratinib, an irreversible ErbB receptor tyrosine kinase inhibitor, in patients with advanced ErbB2-positive breast cancer. J. Clin. Oncol. 28, 1301–1307 (2010). • This phase II, open-label, multicentre trial evaluated the efficacy and safety of neratinib in patients with advanced ErbB2-positive breast cancer with or without prior trastuzumab treatment; neratinib was clinically effective with a manageable toxicity profile in both populations.
  Medline CASGoogle Scholar
• 14. Ustaris F, Saura C, Di Palma J et al. Effective management and prevention of neratinib-induced diarrhea. Am. J. Hematol. Oncol. 11(11), 13–22 (2015). • This review discusses the incidence, severity and patterns of occurrence of diarrhea in patients treated with neratinib, and how this may be effectively managed; intensive loperamide prophylaxis effectively prevents neratinib-related diarrhoea.
  Google Scholar
• 15. Chan A, Ruiz Borrego M, Marx G et al. 73P Effect of diarrheal prophylaxis or dose escalation on neratinib-associated diarrhea and tolerability in patients with HER2+ early-stage breast cancer: final findings from the CONTROL trial Ann. Oncol. 33, S156, Abstract (2022). • This phase 2, international, multi-cohort, open-label trial investigated pre-emptive antidiarrheal prophylaxis in patients with early-stage HR+ HER2+ breast cancer receiving neratinib after adjuvant trastuzumab-based therapy.
  Google Scholar
• 16. Perez EA, Romond EH, Suman VJ et al. Trastuzumab plus adjuvant chemotherapy for human epidermal growth factor receptor 2-positive breast cancer: planned joint analysis of overall survival from NSABP B-31 and NCCTG N9831. J. Clin. Oncol. 32, 3744–3752 (2014).
  Medline CASGoogle Scholar
• 17. Cameron D, Piccart-Gebhart MJ, Gelber RD et al. 11 years' follow-up of trastuzumab after adjuvant chemotherapy in HER2-positive early breast cancer: final analysis of the HERceptin Adjuvant (HERA) trial. Lancet. 389, 1195–1205 (2017).
  Medline CASGoogle Scholar
• 18. Goldhirsch A, Gelber RD, Piccart-Gebhart MJ et al. 2 years versus 1 year of adjuvant trastuzumab for HER2-positive breast cancer (HERA): an open-label, randomised controlled trial. Lancet. 382, 1021–1028 (2013).
  Medline CASGoogle Scholar
• 19. 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. Ann. Oncol. 30, 1541–1557 (2019).
  Medline CASGoogle Scholar
• 20. Chan A, Delaloge S, Holmes FA 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. 17, 367–377 (2016).
  Medline CASGoogle Scholar
• 21. Martin M, Holmes FA, Ejlertsen B et al. Neratinib after trastuzumab-based adjuvant therapy in HER2-positive breast cancer (ExteNET): 5-year analysis of a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 18, 1688–1700 (2017).
  Medline CASGoogle Scholar
• 22. Piccart-Gebhart M, Holmes E, Baselga J et al. Adjuvant lapatinib and trastuzumab for early human epidermal growth factor receptor 2-positive breast cancer: results from the randomized phase III adjuvant lapatinib and/or trastuzumab treatment optimization trial. J. Clin. Oncol. 34, 1034–1042 (2016).
  Medline CASGoogle Scholar
• 23. von Minckwitz G, Procter M, de Azambuja E et al. Adjuvant pertuzumab and trastuzumab in early HER2-positive breast cancer. N. Engl. J. Med. 377, 122–131 (2017).
  Medline CASGoogle Scholar
• 24. von Minckwitz G, Huang CS, Mano MS et al. Trastuzumab emtansine for residual invasive HER2-positive breast cancer. N. Engl. J. Med. 380, 617–628 (2019).
  Medline CASGoogle Scholar
• 25. Earl HM, Hiller L, Vallier AL et al. 6 versus 12 months of adjuvant trastuzumab for HER2-positive early breast cancer (PERSEPHONE): 4-year disease-free survival results of a randomised phase 3 non-inferiority trial. Lancet. 393, 2599–2612 (2019).
  Medline CASGoogle Scholar
• 26. Pivot X, Romieu G, Debled M et al. 6 months versus 12 months of adjuvant trastuzumab in early breast cancer (PHARE): final analysis of a multicentre, open-label, phase 3 randomised trial. Lancet. 393, 2591–2598 (2019).
  Medline CASGoogle Scholar
• 27. Conte P, Frassoldati A, Bisagni G et al. Nine weeks versus 1 year adjuvant trastuzumab in combination with chemotherapy: final results of the phase III randomized Short-HER study‡. Ann. Oncol. 29, 2328–2333 (2018).
  Medline CASGoogle Scholar
• 28. Piccart-Gebhart M, Holmes A, Baselga J et al. First results from the phase III ALTTO trial (BIG 2-06; NCCTG [Alliance] N063D) comparing one year of anti-HER2 therapy with lapatinib alone (L), trastuzumab alone (T), their sequence (T→L), or their combination (T+L) in the adjuvant treatment of HER2-positive early breast cancer (EBC) J. Clin. Oncol. 32(Suppl. 18), Abstract, DOI:10.1200/jco.2014.32.18_suppl.lba4 (2014).
  Google Scholar
• 29. Tolaney SM, Barry WT, Dang CT et al. Adjuvant paclitaxel and trastuzumab for node-negative, HER2-positive breast cancer. N. Engl. J. Med. 372, 134–141 (2015).
  MedlineGoogle Scholar
• 30. Awada A, Colomer R, Inoue K et al. Neratinib plus paclitaxel vs trastuzumab plus paclitaxel in previously untreated metastatic ERBB2-positive breast cancer: the NEfERT-T randomized clinical trial. JAMA. Oncol. 2, 1557–1564 (2016).
  MedlineGoogle Scholar
• 31. Saura C, Oliveira M, Feng YH et al. Neratinib plus capecitabine versus lapatinib plus capecitabine in HER2-positive metastatic breast cancer previously treated with ≥2 HER2-directed regimens: phase III NALA trial. J. Clin. Oncol. 38, 3138–3149 (2020).
  Medline CASGoogle Scholar
• 32. EMA. Nerlynx (2018). www.ema.europa.eu/en/medicines/human/EPAR/nerlynx (Accessed 16 June 2023).
  Google Scholar
• 33. Johnston SR. New strategies in estrogen receptor-positive breast cancer. Clin. Cancer Res. 16, 1979–1987 (2010).
  Medline CASGoogle Scholar
• 34. Montemurro F, Di Cosimo S, Arpino G. Human epidermal growth factor receptor 2 (HER2)-positive and hormone receptor-positive breast cancer: new insights into molecular interactions and clinical implications. Ann. Oncol. 24, 2715–2724 (2013).
  Medline CASGoogle Scholar
• 35. Nagpal A, Redvers RP, Ling X et al. Neoadjuvant neratinib promotes ferroptosis and inhibits brain metastasis in a novel syngeneic model of spontaneous HER2(+ve) breast cancer metastasis. Breast Cancer Res. 21, 94 (2019).
  MedlineGoogle Scholar
• 36. Chan A, Moy B, Mansi J et al. Final efficacy results of neratinib in HER2-positive hormone receptor-positive early-stage breast cancer from the phase III ExteNET trial. Clin. Breast. Cancer. 21, 80–91.e7 (2021).
  Medline CASGoogle Scholar
• 37. Martin Jimenez M, Gnant M, Ejlertsen B et al. 83P Impact of treatment duration of extended adjuvant therapy with neratinib in early stage HER2+ HR+ breast cancer after trastuzumab-based therapy on patient outcomes Ann. Oncol. 31, S43; Abstract (2020).
  Google Scholar
• 38. Olson EM, Abdel-Rasoul M, Maly J, Wu CS, Lin NU, Shapiro CL. Incidence and risk of central nervous system metastases as site of first recurrence in patients with HER2-positive breast cancer treated with adjuvant trastuzumab. Ann. Oncol. 24, 1526–1533 (2013).
  Medline CASGoogle Scholar
• 39. O'Sullivan CC, Ballman KV, McCall L et al. Alliance A011801 (compassHER2-RD): postneoadjuvant TDM1 + tucatinib/placebo in patients with residual HER2-positive invasive breast cancer. Future Oncol. 17, 4665–4676 (2021).
  Google Scholar
• 40. Mortimer J, Di Palma J, Schmid K, Ye Y, Jahanzeb M. Patterns of occurrence and implications of neratinib-associated diarrhea in patients with HER2-positive breast cancer: analyses from the randomized phase III ExteNET trial. Breast Cancer Res. 21, 32 (2019).
  MedlineGoogle Scholar
• 41. Barcenas CH, Hurvitz SA, Di Palma JA et al. Improved tolerability of neratinib in patients with HER2-positive early-stage breast cancer: the CONTROL trial. Ann. Oncol. 31, 1223–1230 (2020).
  Medline CASGoogle Scholar
• 42. Harbeck N, Wrobel D, Zaiss M et al. 75P Interim analysis (n=150) of the multi-national, prospective, non-interventional ELEANOR study observing real-life extended adjuvant treatment with neratinib in patients with HER2+ / HR+ early breast cancer (eBC) Ann. Oncol. 33, S157; Abstract (2022).
  Google Scholar
• 43. Delaloge S, Cella D, Ye Y et al. Effects of neratinib on health-related quality of life in women with HER2-positive early-stage breast cancer: longitudinal analyses from the randomized phase III ExteNET trial. Ann. Oncol. 30, 567–574 (2019).
  Medline CASGoogle Scholar
• 44. de Azambuja E, Ponde N, Procter M et al. A pooled analysis of the cardiac events in the trastuzumab adjuvant trials. Breast Cancer Res. Treat. 179, 161–171 (2020).
  Medline CASGoogle Scholar
• 45. Pinder MC, Duan Z, Goodwin JS et al. Congestive heart failure in older women treated with adjuvant anthracycline chemotherapy for breast cancer. J. Clin. Oncol. 25, 3808–3815 (2007).
  Medline CASGoogle Scholar
• 46. Cardinale D, Colombo A, Bacchiani G et al. Early detection of anthracycline cardiotoxicity and improvement with heart failure therapy. Circulation. 131, 1981–1988 (2015).
  Medline CASGoogle Scholar
• 47. Cardoso F, Kyriakides S, Ohno S et al. Early breast cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up†. Ann. Oncol. 30, 1194–1220 (2019).
  Medline CASGoogle Scholar
• 48. Jacobs SA, Robidoux A, Abraham J et al. NSABP FB-7: a phase II randomized neoadjuvant trial with paclitaxel + trastuzumab and/or neratinib followed by chemotherapy and postoperative trastuzumab in HER2(+) breast cancer. Breast Cancer Res. 21, 133 (2019).
  Medline CASGoogle Scholar
• 49. Park JW, Liu MC, Yee D et al. Adaptive randomization of neratinib in early breast cancer. N. Engl. J. Med. 375, 11–22 (2016).
  Medline CASGoogle Scholar