TNBC: induction with chemotherapy increases response to immunotherapy

  • Voorwerk L & al.
  • Nat Med
  • 13 May 2019

  • curated by Deepa Koli
  • Univadis Clinical Summaries
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  • Short-term doxorubicin and cisplatin induce a more favorable tumor microenvironment and increase response rate to nivolumab in patients with metastatic triple-negative breast cancer (TNBC).

Why this matters

  • TNBC has poor prognosis.
  • Findings suggest tumor microenvironment modulation using low-dose chemotherapy or irradiation prior to programmed cell death protein 1 (PD-1)/ programmed death ligand 1 (PD-L1) blockade may increase the response rate.

Study design

  • Phase 2 TONIC trial: 66 patients with metastatic TNBC were randomly assigned to no induction (n=12) or 2-week induction with either hypofractionated irradiation (n=12), low-dose cyclophosphamide (n=12), cisplatin (n=13) or doxorubicin (n=17).
  • All treatments were followed by nivolumab.
  • Funding: Bristol-Myers-Squibb through the International Immuno-Oncology Network; others.

Key results

  • Median PFS was 1.9 months.
  • Overall objective response rate (ORR) to nivolumab was 20%.
  • Median duration of response was 9 months.
  • Most responses occurred in doxorubicin and cisplatin groups (ORR, 35% and 23%, respectively). 
  • ORR in no induction group was 17%.
  • T-cell receptor clonality and upregulation of inflammation-related signatures were more pronounced with cisplatin and doxorubicin vs no induction cohort.
  • 19 patients (28%) experienced induction treatment-related any grade adverse events (AEs) (grade 3, 3%), and 13 had grade 3-5 immune-related AEs.


  • Study was underpowered for direct comparison of between groups.

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