Developing combination therapies with biologics in triple-negative breast cancer

Expert Opin Biol Ther. 2024 Oct;24(10):1075-1094. doi: 10.1080/14712598.2024.2408756. Epub 2024 Oct 3.

Abstract

Introduction: Novel compounds have entered the triple-negative breast cancer (TNBC) treatment algorithm, namely immune checkpoints inhibitors (ICIs), PARP inhibitors and antibody-drug conjugates (ADCs). The optimization of treatment efficacy can be enhanced with the use of combination treatments, and the incorporation of novel compounds. In this review, we discuss the combination treatments under development for the treatment of TNBC.

Areas covered: The development of new drugs occurring in recent years has boosted the research for novel combinations to target TNBC heterogeneity and improve outcomes. ICIs, ADCs, tyrosine kinase inhibitors (TKIs), and PARP inhibitors have emerged as leading players in this new landscape, while other compounds like novel intracellular pathways inhibitors or cancer vaccines are drawing more and more interest. The future of TNBC is outlined in combination approaches, and based on new cancer targets, including many chemotherapy-free treatments.

Expert opinion: A large number of TNBC therapies have either proved clinically ineffective or weighted by unacceptable safety profiles. Others, however, have provided promising results and are currently in late-stage clinical trials, while a few have actually changed clinical practice in recent years. As novel, more and more selective drugs come up, combination strategies focusing the concept of synergy are fully warranted for the future.

Keywords: ADC; PARP inhibitors; TNBC; Triple negative breast cancer; antibody-drug conjugates; immune checkpoints inhibitors; new drugs.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols* / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols* / therapeutic use
  • Biological Products / adverse effects
  • Biological Products / therapeutic use
  • Female
  • Humans
  • Immune Checkpoint Inhibitors / therapeutic use
  • Immunoconjugates / therapeutic use
  • Poly(ADP-ribose) Polymerase Inhibitors / therapeutic use
  • Triple Negative Breast Neoplasms* / drug therapy

Substances

  • Biological Products
  • Immune Checkpoint Inhibitors
  • Poly(ADP-ribose) Polymerase Inhibitors
  • Immunoconjugates
  • Antineoplastic Agents