ASCO 2020 – Does locoregional therapy really offer benefit in de novo stage IV breast cancer?

  • Daniela Ovadia — Agenzia Zoe
  • Oncology Conference reports
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  • Early locoregional therapy (LRT; e.g., surgery and/or radiotherapy) does not improve survival in patients with de novo metastatic breast cancer and an intact primary tumor (IPT).
  • Despite a 2.5-fold higher risk for local disease progression without LRT, the therapy did not lead to improved QoL.
  • LRT may be considered when systemic disease is well-controlled with systemic therapy but the primary site is progressing.

Why this matters

  • About 6% (10%-20% in resource-constrained countries) of patients with newly diagnosed breast cancer present with stage IV disease and an IPT.
  • LRT for patients with IPT is hypothesized to improve survival based on retrospective studies.
    • According to the current authors, however, these studies were biased: women undergoing surgery were younger and had smaller tumors, more ER+ disease, and lower metastatic burden.

Study design

  • Patients with stage IV disease and IPT were registered in a phase 3 trial and treated with optimal systemic therapy (OST) based on patient and tumor characteristics.
  • Those who did not progress during 4-8 months of OST were randomly allocated to LRT or no LRT.
  • 390 patients were enrolled.
    • 256 eligible patients were randomly assigned to either continued OST alone (n=131) or OST+LRT (n=125).
  • The primary endpoint was OS, with locoregional disease control as a secondary endpoint.
  • Funding: NIH.

Key results

  • There were 121 deaths and 43 locoregional progression events after a median follow-up of 59 (range, 0-91) months.
  • No significant difference in 3-year OS rate:
    • 68.4% with OST+LRT vs 67.9% OST alone; 
    • Stratified log-rank P=.63. 
  • No difference in PFS (P=.40).
  • 3-year locoregional recurrence/progression rate was significantly higher in the OST-alone group: 25.6% vs 10.2% with OST+LRT (P=.003).
  • Health-related QoL measured using the FACT-B Trial Outcome Index was significantly worse in the OST+LRT group vs OST-alone group at 18 months after randomization.
    • However, no difference was observed at 6 months (74% completion) or 30 months (56% completion).
  • Data from the ongoing Japanese JCOG 1017 study with a similar design are expected to confirm the outcomes.


  • Results presented without peer review at a conference.

Expert commentary

  • “Even if locoregional therapy doesn’t improve the quality of life and survival, 20% of the patients will need surgery for palliation at some point," said Julia R. White, a radiation oncologist at The Ohio State University. "There are other trials with different results, notably the Multi-center Turkish Federation trial, that shows an improved overall survival at 5 years especially in patients with solitary bone metastasis.
  • "Ongoing clinical trials will tell us if there is a subgroup of patients that can benefit from a combination of LRT and systemic therapy,” she added.