- 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.
- 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.
- 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.
- “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.