Identification of early breast cancer patient cohorts who may benefit from lapatinib therapy Academic Article uri icon

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abstract

  • In resource-constrained environments many patients with human epidermal growth factor receptor 2 (HER2)+ early breast cancer are currently not offered adjuvant anti-HER2 therapy. For patients who might be able to receive the tyrosine kinase inhibitor (TKI) lapatinib (e.g. after patent expiration), it is important to identify subgroups of patients for whom anti-HER2 TKI therapy could be beneficial. To do this, we used data from 2489 patients with centrally confirmed HER2+ disease enrolled in the adjuvant Tykerb Evaluation After Chemotherapy (TEACH) trial, investigating the effect of lapatinib in patients with HER2+ early breast cancer not treated with trastuzumab. We performed subgroup analyses and number-needed-to-treat (NNT) calculations using patient and tumour associated predictors. Hormone receptor negative (HR-) patients on lapatinib had a significantly prolonged disease-free survival (DFS) compared to HR- patients on placebo (hazard ratio 0.64, P=0.003). For patients with HR- disease, starting treatment with lapatinib ≤1 year from diagnosis improved DFS by 12.1% [2.1-22.1] at 2 years and 15.7% [4.1-27.2] at 5 years. Depending on lymph node status and time since diagnosis the NNT for recurrence (at 5 years) was between 5.9 (node positive patients <1 year from diagnosis) and 15.9. These numbers are in range with numbers reported for up-front adjuvant trastuzumab for HR unselected patients (e.g. 15.6 for DFS at 4 years in HERA). In a subgroup analysis of the adjuvant TEACH trial, we show that anti-HER2 monotherapy with a TKI is beneficial as adjuvant therapy in a subgroup of patients. NNT in HER2+ HR- patients are in range with those reported from up-front adjuvant trastuzumab trials.

authors

  • Strasser-Weippl, Kathrin
  • Horick, Nora
  • Smith, Ian E
  • O'Shaughnessy, Joyce
  • Ejlertsen, Bent
  • Boyle, Frances
  • Buzdar, Aman U
  • Fumoleau, Pierre
  • Gradishar, William
  • Martin, Miguel
  • Moy, Beverly
  • Piccart-Gebhart, Martine
  • Pritchard, Kathleen
  • Lindquist, Deborah
  • Rappold, Erica
  • Finkelstein, Dianne M
  • Goss, Paul E

publication date

  • March 2016

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