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Immune induction strategies to enhance responses to PD-1 blockade: lessons from the TONIC trial

Sandra Demaria1,2, Emanuela Romano3, Muriel Brackstone4

  • 1Department of Radiation Oncology, Weill Cornell Medicine, 1300 York Ave, Box 169, New York, NY, 10065, USA. szd3005@med.cornell.edu.

Journal for Immunotherapy of Cancer
|November 23, 2019
PubMed

Insights

Doxorubicin induction therapy improved tumor immune microenvironment and enhanced responses to PD-1 blockade in metastatic triple-negative breast cancer. This adaptive trial identified doxorubicin as a promising combination for future immunotherapy studies.

Area of Science:

  • Immunotherapy
  • Oncology
  • Clinical Trials

Background:

  • Programmed cell death protein 1 (PD-1) blockade shows limited efficacy in many patients, necessitating combination therapies.
  • Metastatic triple-negative breast cancer has a poor response rate to PD-1 blockade, highlighting the need for improved treatment strategies.

Purpose of the Study:

  • To accelerate the identification of effective combination therapies for PD-1 blockade.
  • To evaluate short-course induction therapies for their ability to enhance anti-tumor immune responses and improve outcomes in metastatic triple-negative breast cancer.

Main Methods:

  • An adaptive trial design was employed to compare four induction therapies: radiotherapy, cyclophosphamide, cisplatin, and doxorubicin.
  • The trial enrolled 12-17 patients per arm in its initial phase to select the most promising treatment for further investigation.
  • Tumor immune microenvironment changes and objective response rates (ORR) were assessed following induction therapy and subsequent PD-1 blockade.

Main Results:

  • Doxorubicin induction therapy demonstrated higher objective response rates compared to no induction therapy.
  • The doxorubicin arm was selected to advance to phase II of the adaptive trial.
  • Other induction therapies did not show significant improvement in response rates in this initial phase.

Conclusions:

  • Doxorubicin is a potential candidate for combination therapy to enhance PD-1 blockade efficacy in metastatic triple-negative breast cancer.
  • Adaptive trial designs can efficiently identify promising induction treatments for immunotherapy combinations.
  • Further research is needed to optimize the sequencing and type of induction therapies used in combination with PD-1 blockade.
Keywords:
Immunogenic cell death, tumor burdenImmunomodulationTumor-infiltrating T cells

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