Efficacy of tucatinib for HER2-positive metastatic breast cancer after HER2-targeted therapy: a network meta-analysis

Future Oncol. 2021 Nov;17(33):4635-4647. doi: 10.2217/fon-2021-0742. Epub 2021 Aug 31.

Abstract

Aim: A systematic literature review and network meta-analysis of randomized controlled trials in patients receiving therapy for HER2+ unresectable/metastatic breast cancer after ≥1 HER2-directed therapy was conducted to compare progression-free survival (PFS) and overall survival (OS). Methods: Hazard ratios (HRs) and relative differences from fractional polynomials (FPs) for PFS and OS were assessed by Bayesian network meta-analyses. Results: For PFS, surface under the cumulative rankogram (SUCRA) ranked tucatinib plus trastuzumab with capecitabine as highest in both HR and FP analyses, followed by T-DM1 monotherapy and neratinib plus capecitabine. For OS, SUCRA ranked tucatinib plus trastuzumab with capecitabine as highest in both HR and FP analyses, followed by pertuzumab plus trastuzumab with capecitabine and T-DM1 monotherapy, with similar scores. Conclusion: Tucatinib plus trastuzumab with capecitabine, and T-DM1 monotherapy, consistently showed improved PFS and OS versus lapatinib/trastuzumab plus capecitabine and non-targeted treatments.

Keywords: human epidermal growth factor receptor 2; metastatic breast cancer; network meta-analysis; overall survival; progression-free survival; second-line; third-line.

Plain language summary

Lay abstract Although several therapies are used in HER2-positive metastatic breast cancer, direct head-to-head comparisons of these therapies are lacking. We conducted a network meta-analysis, a way of indirectly comparing the results of different clinical trials, to compare how long patients receiving therapy had no disease progression, and also how long patients survived. In terms of avoiding disease progression, tucatinib plus trastuzumab with capecitabine ranked highest, followed by T-DM1 monotherapy and neratinib plus capecitabine. In terms of survival, tucatinib plus trastuzumab with capecitabine ranked highest, followed by pertuzumab plus trastuzumab with capecitabine and T-DM1. Tucatinib in combination with trastuzumab plus capecitabine and also T-DM1 monotherapy consistently demonstrated improved progression-free and overall survival outcomes compared with other therapies.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Ado-Trastuzumab Emtansine / pharmacology
  • Ado-Trastuzumab Emtansine / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / mortality
  • Breast Neoplasms / pathology
  • Capecitabine / pharmacology
  • Capecitabine / therapeutic use
  • Drug Resistance, Neoplasm
  • Female
  • Humans
  • Oxazoles / pharmacology
  • Oxazoles / therapeutic use*
  • Progression-Free Survival
  • Pyridines / pharmacology
  • Pyridines / therapeutic use*
  • Quinazolines / pharmacology
  • Quinazolines / therapeutic use*
  • Quinolines / pharmacology
  • Quinolines / therapeutic use
  • Receptor, ErbB-2 / analysis
  • Receptor, ErbB-2 / antagonists & inhibitors*
  • Receptor, ErbB-2 / metabolism
  • Trastuzumab / pharmacology
  • Trastuzumab / therapeutic use

Substances

  • Oxazoles
  • Pyridines
  • Quinazolines
  • Quinolines
  • tucatinib
  • Capecitabine
  • ERBB2 protein, human
  • Receptor, ErbB-2
  • neratinib
  • Trastuzumab
  • Ado-Trastuzumab Emtansine

Grants and funding